Human Serum Amyloid P Component is a Single Uncomplexed Pentamer in Whole Serum
Open accessAbstract
BACKGROUND: Serum amyloid P component (SAP) is a universal constituent of amyloid deposits and contributes to their pathogenesis. SAP also has important normal functions in the handling of chromatin in vivo and resistance to bacterial infection. The atomic resolution crystal structure of SAP is known, but its physiological oligomeric assembly remains controversial. In the absence of calcium, isolated human SAP forms stable decamers composed of two cyclic disk-like pentamers interacting face to face. However, in the presence of its specific low molecular weight ligands and calcium, SAP forms stable pentamers. In the presence of calcium, but without any ligand, isolated human SAP aggressively autoaggregates and precipitates, imposing severe constraints on methods for molecular mass determination. MATERIALS AND METHODS: Gel filtration chromatography and density gradient ultracentrifugation were used to compare SAP with the closely related molecule, C-reactive protein (CRP; which is known to be a single pentamer) and the effect of human serum albumin on SAP autoaggregation was investigated. RESULTS: In most physiological buffers and with the necessary absence of calcium, SAP, whether isolated or from whole serum samples, eluted from gel filtration columns clearly ahead of CRP. This is consistent with the existence of a monodisperse population of SAP decamers, as previously reported. However, in Tris/phosphate buffer, SAP was pentameric, suggesting that decamerization involved ionic interactions. On density gradients formed in undiluted normal human serum, SAP sedimented as single pentamers not complexed with any macromolecular ligand, regardless of the presence or absence of calcium. The calcium-dependent autoaggregation of isolated SAP was completely inhibited by physiological concentrations of albumin and the SAP remained pentameric. CONCLUSIONS: Human SAP exists within serum as single uncomplexed pentamers in the presence or absence of calcium. This oligomeric assembly, thus, does not require a calcium-dependent small molecule interaction. The usual >2000-fold molar excess of albumin over SAP in plasma is apparently sufficient to keep SAP in its physiological conformation.
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SAP/PTX2 is primarily produced in the liver in physiological conditions in humans.
“Previous studies have shown that SAP/PTX2 is primarily produced in the liver in physiological conditions in humans81–83.”
From Serum amyloid P secreted by bone marrow adipocytes drives skeletal amyloidosis (2025) · cites this paper as [82]
The Introduction describes human SAP as a normal plasma glycoprotein, and the methods examine SAP in human serum. Neither those passages nor searches for liver, hepatic synthesis, and hepatocytes address where SAP is produced or whether the liver is its primary source under physiological conditions. (LLM, conf=0.76)
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Cites
Pepys, M., & Baltz, M. (1983) · Advances in Immunology · doi:10.1016/s0065-2776(08)60379-x · Cited by 1,322 · cited 1× · see citing works
“dependent ligand binding plasma proteins (1).”
Self-citationThe physiological structure of human C-reactive protein and its complex with phosphocholine
Thompson, D., Pepys, M. B., & Wood, S. P. (1999) · Structure · doi:10.1016/s0969-2126(99)80023-9 · Cited by 818 · cited 1× · see citing works
“Intact native CRP is known from previous gel filtration, ultracentrifuge, X-ray and neutron solution scattering studies to be a pentamer (14,35,45), and its crystal structure confirms the electron microscopic appearance of cyclic pentameric arrangement of the protomers (2,8,10,46,47).”
BackgroundSelf-citationVigushin, D., Pepys, M., & Hawkins, P. (1993) · Journal of Clinical Investigation · doi:10.1172/jci116336 · Cited by 681 · cited 1× · see citing works
“The protomers of human CRP are non-glycosylated and have an Mr of 23,027, as predicted by the amino acid sequence and confirmed by ESIMS measurement (44).”
MethodSelf-citationSerum amyloid P component controls chromatin degradation and prevents antinuclear autoimmunity
Bickerstaff, M., Botto, M., Hutchinson, W., Herbert, J., Tennent, G., Bybee, A., Mitchell, D., Cook, H., Butler, P., Walport, M., et al. (1999) · Nature Medicine · doi:10.1038/9544 · Cited by 548 · cited 1× · see citing works
“Recently, we found that SAP knockout mice spontaneously developed severe antinuclear autoimmunity and glomerulonephritis, as well as altered innate resistance to bacterial infection (26,27).”
BackgroundSelf-citationStructure of pentameric human serum amyloid P component
Emsley, J., White, H., O'Hara, B., Oliva, G., Srinivasan, N., Tickle, I., Blundell, T., Pepys, M., & Wood, S. (1994) · Nature · doi:10.1038/367338a0 · Cited by 488 · cited 3× · see citing works
“Molecular Medicine 6(6): 482–493, 2000”
BackgroundSelf-citationTennent, G. A., Lovat, L. B., & Pepys, M. B. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.10.4299 · Cited by 438 · see citing works
Self-citationOsmand, A., Friedenson, B., Gewurz, H., Painter, R. H., Hofmann, T., & Shelton, E. (1977) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.74.2.739 · Cited by 350 · cited 1× · see citing works
“Intact native CRP is known from previous gel filtration, ultracentrifuge, X-ray and neutron solution scattering studies to be a pentamer (14,35,45), and its crystal structure confirms the electron microscopic appearance of cyclic pentameric arrangement of the protomers (2,8,10,46,47).”
BackgroundThree dimensional structure of human C-reactive protein
Shrive, A., Gheetham, G. M. T., Holden, D., Myles, D., Turnell, W., Volanakis, J., Pepys, M., Bloomer, A., & Greenhough, T. (1996) · Nature Structural Biology · doi:10.1038/nsb0496-346 · Cited by 349 · cited 1× · see citing works
“Intact native CRP is known from previous gel filtration, ultracentrifuge, X-ray and neutron solution scattering studies to be a pentamer (14,35,45), and its crystal structure confirms the electron microscopic appearance of cyclic pentameric arrangement of the protomers (2,8,10,46,47).”
BackgroundSelf-citationAmyloid deposition is delayed in mice with targeted deletion of the serum amyloid P component gene
Botto, M., Hawkins, P. N., Bickerstaff, M. C. M., Herbert, J., Bygrave, A. E., Mcbride, A., Hutchinson, W. L., Tennent, G. A., Walportz, M. J., & Pepys, M. B. (1997) · Nature Medicine · doi:10.1038/nm0897-855 · Cited by 266 · see citing works
Self-citationPepys, M., Rademacher, T., Amatayakul-Chantler, S., Williams, P., Noble, G. E., Hutchinson, W., Hawkins, P. N., Nelson, S. R., Gallimore, J., & Herbert, J. (1994) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.91.12.5602 · Cited by 217 · cited 1× · see citing works
“The protomer mass of human SAP is 25,462 D, as predicted by the amino acid and complete, invariant, glycan sequence, and confirmed by electrospray ionization mass spectrometry (ESIMS) measurement (43).”
BackgroundSelf-citationPepys, M., Dash, A., Fletcher, T. C., Richardson, N., Munn, E., & Feinstein, A. (1978) · Nature · doi:10.1038/273168a0 · Cited by 200 · cited 2× · see citing works
“Intact native CRP is known from previous gel filtration, ultracentrifuge, X-ray and neutron solution scattering studies to be a pentamer (14,35,45), and its crystal structure confirms the electron microscopic appearance of cyclic pentameric arrangement of the protomers (2,8,10,46,47).”
BackgroundSelf-citationSerum amyloid P component is the major calcium-dependent specific DNA binding protein of the serum.
Pepys, M., & Butler, P. (1987) · Biochemical and Biophysical Research Communications - BBRC · doi:10.1016/0006-291x(87)91111-9 · Cited by 191 · see citing works
Self-citationAmyloid P component. A critical review
Pepys, M. B., Booth, D. R., Hutchinson, W. L., Gallimore, J. R., Collins, I. M., & Hohenester, E. (1997) · Amyloid · doi:10.3109/13506129709003838 · Cited by 181 · cited 2× · see citing works
“Analysis of the packing of SAP pentamers in several unrelated crystal forms suggests that Glu167, the side chain of which protrudes from the N-terminus of the -helix on the A face, is the structure responsible (18).”
BackgroundSelf-citationFibronectin and C4-binding protein are selectively bound by aggregated amyloid P component
de Beer, F., Baltz, M., Holford, S., Feinstein, A., & Pepys, M. (1981) · Journal of Experimental Medicine · doi:10.1084/jem.154.4.1134 · Cited by 161 · cited 3× · see citing works
“Furthermore, once it is aggregated, human SAP acquires avid and specific binding to plasma fibronectin and C4-binding protein, interactions not shown at all by nonaggregated SAP (29).”
BackgroundResultSelf-citationPepys, M., Dash, A., Munn, E., Feinstein, A., Skinner, M., Cohen, A. B., Gewurz, H., Osmand, A., & Painter, R. H. (1977) · The Lancet · doi:10.1016/s0140-6736(77)91260-0 · Cited by 160 · see citing works
Self-citationPHYLOGENETIC ASPECTS OF C‐REACTIVE PROTEIN AND RELATED PROTEINS *
Baltz, M., de Beer, F., Feinstein, A., Munn, E., Milstein, C., Fletcher, T. C., March, J., Taylor, J., Bruton, C., Clamp, J. R., et al. (1982) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1982.tb22125.x · Cited by 157 · cited 1× · see citing works
“indicating that they have important functions (2,3).”
Self-citationWoo, P., Korenberg, J., & Whitehead, A. (1985) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)38881-6 · Cited by 156 · cited 1× · see citing works
“Human SAP and CRP have 51% strict residue-for-residue sequence homology, rising to 66% when conservative substitutions are taken into account (4,5).”
BackgroundBinding specificity of serum amyloid P component for the pyruvate acetal of galactose
Hind, C., Collins, P., Renn, D., Cook, R., Caspi, D., Baltz, M., & Pepys, M. (1984) · Journal of Experimental Medicine · doi:10.1084/jem.159.4.1058 · Cited by 127 · cited 3× · see citing works
“FPLC gel filtration of SAP in the presence of 2 mM calcium and 10 mM MO DG, the bestcharacterized, calcium-dependent carbohydrate ligand of SAP (39), gave an elution volume (Ve) value very close to that of CRP.”
BackgroundMethodInfluentialSelf-citationIsolation of human C-reactive protein and serum amyloid P component.
de Beer, F. D., & Pepys, M. (1982) · JIM - Journal of Immunological Methods · doi:10.1016/0022-1759(82)90300-3 · Cited by 119 · cited 1×
“Intact native CRP is known from previous gel filtration, ultracentrifuge, X-ray and neutron solution scattering studies to be a pentamer (14,35,45), and its crystal structure confirms the electron microscopic appearance of cyclic pentameric arrangement of the protomers (2,8,10,46,47).”
BackgroundSelf-citationAshton, A. W., Boehm, M., Gallimore, J., Pepys, M., & Perkins, S. J. (1997) · Journal of Molecular Biology · doi:10.1006/jmbi.1997.1271 · Cited by 118 · cited 4× · see citing works
“Solution scattering studies, coupled with the crystal structure of SAP, strongly suggest that the stable SAP decamer seen in calciumfree solution is formed by the stacking face-toface of the so-called A surfaces of the pentamers, which are those bearing the -helix of each protomer (15).”
BackgroundInfluentialSelf-citationButler, P., Tennent, G., & Pepys, M. (1990) · Journal of Experimental Medicine · doi:10.1084/jem.172.1.13 · Cited by 112 · cited 1× · see citing works
“The calcium-dependent autoaggregation of isolated SAP, which is completely inhibited by calcium-dependent ligands, including MO DG, phosphoethanolamine, dAMP, DNA, and glycosaminoglycans (23,42,49), probably reflects binding by the ligand-binding pocket(s) of one SAP molecule to a structure on another, leading to latt…”
BackgroundSelf-citationHawkins, P. N., Wootton, R., & Pepys, M. (1990) · Journal of Clinical Investigation · doi:10.1172/jci114917 · Cited by 102 · see citing works
Self-citationSchwalbe, R. A., Dahlbäck, B., & Nelsestuen, G. (1990) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)45804-8 · Cited by 97 · see citing works
Hind, C., Collins, P., Baltz, M., & Pepys, M. (1985) · Biochemical Journal · doi:10.1042/bj2250107 · Cited by 92 · cited 1×
“SAP is also a lectin that binds to various bacteria (25).”
BackgroundSelf-citationSerum amyloid P component in chronic renal failure and dialysis.
Nelson, S. R., Tennent, G., Sethi, D., Gower, P., Ballardie, F. W., Amatayakul-Chantler, S., & Pepys, M. (1991) · Clinica chimica acta; international journal of clinical chemistry · doi:10.1016/0009-8981(91)90090-y · Cited by 91 · cited 1× · see citing works
“SAP, CRP and mouse C3 were quantified by electroimmunoassay using monospecific sheep antisera and serum standards previously calibrated against the isolated pure proteins (36, 40,41).”
MethodSelf-citationComparative analyses of pentraxins: implications for protomer assembly and ligand binding.
Srinivasan, N., White, H., Emsley, J., Wood, S., Pepys, M., & Blundell, T. (1995) · Structure · doi:10.1016/s0969-2126(94)00105-7 · Cited by 88 · see citing works
Self-citationMantzouranis, E. C., Dowton, S., Whitehead, A., Edge, M., Bruns, G., & Colten, H. (1985) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)39671-0 · Cited by 77 · cited 1×
“Human SAP and CRP have 51% strict residue-for-residue sequence homology, rising to 66% when conservative substitutions are taken into account (4,5).”
BackgroundSerum Amyloid P Component Binding to C4b-binding Protein (*)
de Frutos, P. G., Härdig, Y., & Dahlbäck, B. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.45.26950 · Cited by 76 · see citing works
Breathnach, S., Kofler, H., Sepp, N., Ashworth, J., Woodrow, D., Pepys, M., & Hintner, H. (1989) · Journal of Experimental Medicine · doi:10.1084/jem.170.4.1433 · Cited by 76 · see citing works
Self-citationHawkins, P., Tennent, G., Woo, P., & Pepys, M. (1991) · Clinical and Experimental Immunology · doi:10.1111/j.1365-2249.1991.tb08166.x · Cited by 75 · cited 1× · see citing works
“SAP was oxidatively iodinated using N-bromosuccinimide (Sigma, Poole, Dorset, U.K.) (37) and functional integrity of the labeled protein was demonstrated by full retention of its capacity for calcium-dependent binding to phosphoethanolamine covalently immobilized on Sepharose® (Pharmacia Biotech, St. Albans, Herts., U…”
MethodSelf-citationUse of n-Bromosuccinimide for the Iodination of Proteins for Radioimmunoassay
Reay, P. (1982) · Annals of Clinical Biochemistry · doi:10.1177/000456328201900214 · Cited by 54 · cited 1×
“) (37) and functional integrity of the labeled protein was demonstrated by full retention of its capacity for calcium-dependent binding to phosphoethanolamine covalently immobilized on Sepharose® (Pharmacia Biotech, St.”
de Frutos, P. G., & Dahlbäck, B. (1994) · Journal of Immunology · doi:10.4049/jimmunol.152.5.2430 · Cited by 51
Localization of the phosphocholine-binding sites on C-reactive protein by immunoelectron microscopy.
Roux, K. H., Kilpatrick, J., Volanakis, J., & Kearney, J. F. (1983) · Journal of Immunology · doi:10.4049/jimmunol.131.5.2411 · Cited by 50 · cited 1× · see citing works
“Intact native CRP is known from previous gel filtration, ultracentrifuge, X-ray and neutron solution scattering studies to be a pentamer (14,35,45), and its crystal structure confirms the electron microscopic appearance of cyclic pentameric arrangement of the protomers (2,8,10,46,47).”
BackgroundCrystal structure of a decameric complex of human serum amyloid P component with bound dAMP.
Hohenester, E., Hutchinson, W., Pepys, M., & Wood, S. P. (1997) · Journal of Molecular Biology · doi:10.1006/jmbi.1997.1075 · Cited by 49 · cited 3× · see citing works
“The calcium-dependent autoaggregation of isolated SAP, which is completely inhibited by calcium-dependent ligands, including MO DG, phosphoethanolamine, dAMP, DNA, and glycosaminoglycans (23,42,49), probably reflects binding by the ligand-binding pocket(s) of one SAP molecule to a structure on another, leading to latt…”
BackgroundSelf-citationPinteric, L., & Painter, R. H. (1979) · Canadian Journal of Biochemistry · doi:10.1139/o79-091 · Cited by 48 · cited 1×
“Analysis of its oligomeric assembly and binding reactions is greatly complicated by the fact that, uniquely among pentraxins, isolated human SAP undergoes rapid autoaggegration when exposed to calcium (13,28).”
BackgroundPinteric, L., Assimeh, S. N., Kells, D., & Painter, R. H. (1976) · Journal of Immunology · doi:10.4049/jimmunol.117.1.79 · Cited by 47
Calcium-dependent aggregation of human serum amyloid P component.
Baltz, M., de Beer, F. D., Feinstein, A., & Pepys, M. (1982) · Biochimica et Biophysica Acta · doi:10.1016/0167-4838(82)90118-2 · Cited by 46 · cited 5×
“Furthermore, the sedimentation behavior of SAP from serum is unaffected by total depletion of either C4-binding protein or fibronectin from the serum (28).”
BackgroundInfluentialSelf-citationWood, S., Oliva, G., O'Hara, B., White, H., Blundell, T. L., Perkins, S. J., Sardharwalla, I., & Pepys, M. (1988) · Journal of Molecular Biology · doi:10.1016/0022-2836(88)90529-3 · Cited by 35 · cited 1× · see citing works
“Interestingly, this result had been suggested earlier, when SAP was found to be pentameric in the low pH, high acetate, high calcium buffer from which it was originally crystallized for X-ray analysis (48), and the calcium-binding ligand pockets of each protomer were occupied by acetate (6).”
BackgroundSelf-citationHintner, H., Booker, J., Ashworth, J., Auböck, J., Pepys, M., & Breathnach, S. (1988) · Journal of Investigative Dermatology · doi:10.1111/1523-1747.ep12463283 · Cited by 34 · see citing works
Self-citationNative Human Serum Amyloid P Component is a Single Pentamer
Sørensen, I. J., Andersen, O., Nielsen, E. H., & Svehag, S. (1995) · Scandinavian Journal of Immunology · doi:10.1111/j.1365-3083.1995.tb03562.x · Cited by 31 · cited 3× · see citing works
“(16) reported, on the basis of gel filtration studies, that SAP is pentameric in serum.”
BackgroundInfluentialHeparin influence on the complex of serum amyloid P component and complement C4b-binding protein.
Schwalbe, R. A., Dahlbäck, B., & Nelsestuen, G. (1991) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)98779-x · Cited by 23
Hind, C., Collins, P., & Pepys, M. (1984) · Biochimica et Biophysica Acta · doi:10.1016/0304-4165(84)90045-x · Cited by 21 · cited 1×
“The calcium-dependent autoaggregation of isolated SAP, which is completely inhibited by calcium-dependent ligands, including MO DG, phosphoethanolamine, dAMP, DNA, and glycosaminoglycans (23,42,49), probably reflects binding by the ligand-binding pocket(s) of one SAP molecule to a structure on another, leading to latt…”
BackgroundSelf-citation
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Research works printed but not linked: 5
- Perkins SJ, Pepys MB. (1986) X-ray and neutron scattering studies on CRP and SAP. In: Peeters J (ed). Protides of the Biological Fluids, Vol. 34. Perga- mon Press, Oxford, pp. 323-326.
- Pepys MB. (1994) Amyloidosis. In: Frank MM, Austen KF, Claman HN, Unanue ER (eds). Samter's Immunologic Diseases, Fifth Ed. Little, Brown and Company, Boston, pp. 637-655.
- Pepys MB. (1999) The Lumleian Lecture. C- reactive protein and amyloidosis: from proteins to drugs? In: Williams G (ed). Horizons in Medi- cine, Vol. 10. Royal College of Physicians, Lon- don, pp. 397-414.
- Osmand AP, Friedenson B, Gewurz H, Painter RH, Hofmann T, Shelton E. (1977) Characterisa- tion of C-reactive protein and the complement subcomponent Clt as homologous proteins dis- playing cyclic pentameric symmetry (pentrax- ins). Proc. Natl. Acad. Sci. USA 74: 739-743.
- Booth DR, Gallimore JR, Hutchinson WL, et al. (1999) Analysis of autoaggregation and ligand binding sites of serum amyloid P component by in vitro mutagenesis. In: Kyle RA, Gertz MA (eds). Amyloid and Amyloidosis 1998. Parthenon Publishing, Pearl River, New York, pp. 23-25.
Cited by
Sorted by citations
Garlanda, C., Bottazzi, B., Bastone, A., & Mantovani, A. (2005) · Annual Review of Immunology · doi:10.1146/annurev.immunol.23.021704.115756 · Cited by 885 · see citing works
Targeted pharmacological depletion of serum amyloid P component for treatment of human amyloidosis
Pepys, M. B., Herbert, J., Hutchinson, W. L., Tennent, G. A., Lachmann, H. J., Gallimore, J. R., Lovat, L. B., Bartfai, T., Alanine, A., Hertel, C., et al. (2002) · Nature · doi:10.1038/417254a · Cited by 540 · see citing works
“Gel filtration analysis to determine the molecular assembly of SAP–CPHPC complexes was performed as reported elsewher”
MethodSelf-citationInhibition of Fibrocyte Differentiation by Serum Amyloid P 1
Pilling, D., Buckley, C., Salmon, M., & Gomer, R. (2003) · Journal of Immunology · doi:10.4049/jimmunol.171.10.5537 · Cited by 331 · see citing works
“Serum and purified proteins were diluted to 1/1000 in TBS-4% BSA, to prevent SAP from aggregating (15), and incubated for 60 min at 37C.”
MethodReduction of Bleomycin-Induced Pulmonary Fibrosis by Serum Amyloid P
Pilling, D., Roife, D., Wang, M., Ronkainen, S. D., Crawford, J. R., Travis, E. L., & Gomer, R. H. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.179.6.4035 · Cited by 230 · see citing works
“the blood, and circulates as stable 135-kDa pentamers (23, 24).”
BackgroundSerum Amyloid P Inhibits Fibrosis Through FcγR-Dependent Monocyte-Macrophage Regulation in Vivo
Castano, A., Lin, S.-L., Surowy, T., Nowlin, B. T., Turlapati, S. A., Patel, T., Singh, A., Li, S. S., Lupher, M., & Duffield, J. (2009) · Science Translational Medicine · doi:10.1126/scitranslmed.3000111 · Cited by 219 · see citing works
“SAP is produced in the liver and circulates as a highly stable 135-kD pentamer (18) composed of five noncovalently linked 27-kD protomers associated into a ring-like structure (19).”
BackgroundNoursadeghi, M., Bickerstaff, M., Gallimore, J., Herbert, J., Cohen, J., & Pepys, M. (2000) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.97.26.14584 · Cited by 162 · see citing works
Self-citationRole of neoplastic monocyte-derived fibrocytes in primary myelofibrosis
Verstovšek, S., Manshouri, T., Pilling, D., Bueso-Ramos, C., Newberry, K. J., Prijić, S., Knez, L., Božinović, K., Harris, D., Spaeth, E. L., et al. (2016) · The Journal of Experimental Medicine · doi:10.1084/jem.20160283 · Cited by 161 · see citing works
“Notably, the differentiation of monocytes into fibrocytes is inhibited by the pentraxin protein serum amyloid P (SAP) component (pentraxin-2), a 125-kD protein produced by the liver (Steel and Whitehead, 1994; Hutchinson et al., 2000), repeated injections of which have been shown to ameliorate fibrosis in multiple org…”
BackgroundAggregated IgG inhibits the differentiation of human fibrocytes
Pilling, D., Tucker, N. M., & Gomer, R. (2006) · Journal of Leukocyte Biology · doi:10.1189/jlb.0805456 · Cited by 116 · see citing works
“SAP, a member of the pentraxin family of proteins, which includes C-reactive protein (CRP), is produced by the liver, secreted into the blood, and circulates in the blood as stable pentamers [20–23].”
BackgroundIdiopathic pulmonary fibrosis: Molecular mechanisms and potential treatment approaches
Glass, D. S., Grossfeld, D. J., Renna, H. A., Agarwala, P., Spiegler, P. A., Kasselman, L. J., Glass, A. D., DeLeon, J. R., & Reiss, A. B. (2020) · Respiratory Investigation · doi:10.1016/j.resinv.2020.04.002 · Cited by 123 · see citing works
Pentraxins: structure, function, and role in inflammation.
du Clos, T. W. (2013) · ISRN Inflammation · doi:10.1155/2013/379040 · Cited by 96 · see citing works
“Although it was a long held belief that CRP was composed of a single pentamer whereas SAP existed as a decamer, it was later determined that SAP, like CRP, circulates in blood as a single pentamer [4].”
BackgroundThe Development of Serum Amyloid P as a Possible Therapeutic
Pilling, D., & Gomer, R. H. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.02328 · Cited by 92 · see citing works
“SAP is made by hepatocytes and secreted into the blood (1, 2).”
BackgroundSerum amyloid P: a systemic regulator of the innate immune response
Cox, N., Pilling, D., & Gomer, R. (2014) · Journal of Leukocyte Biology · doi:10.1189/jlb.1mr0114-068r · Cited by 89 · see citing works
Molecular dissection of Alzheimer's disease neuropathology by depletion of serum amyloid P component
Kolstoe, S., Ridha, B., Bellotti, V., Wang, N., Robinson, C., Crutch, S., Keir, G., Kukkastenvehmas, R., Gallimore, J., Hutchinson, W., et al. (2009) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.0902640106 · Cited by 74 · see citing works
“The column was calibrated with standard globular markers and with human SAP in a known decameric assembly and the closely related pentraxin protein, human C-reactive protein, which is known to be a single pentamer (37).”
BackgroundMethodSelf-citationThe Pentraxins 1975–2018: Serendipity, Diagnostics and Drugs
Pepys, M. B. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.02382 · Cited by 67 · see citing works
“This is prevented by the presence of physiological concentrations of serum albumin (15), probably, at least in part, by virtue of calcium binding by the albumin, critically lowering the free ionisable calcium concentration.”
BackgroundInfluentialSelf-citationSerum amyloid P inhibits dermal wound healing
Naik-Mathuria, B., Pilling, D., Crawford, J. R., Gay, A. N., Smith, C., Gomer, R., & Olutoye, O. (2008) · Wound Repair and Regeneration · doi:10.1111/j.1524-475x.2008.00366.x · Cited by 61 · see citing works
FcγRI mediates serum amyloid P inhibition of fibrocyte differentiation
Crawford, J. R., Pilling, D., & Gomer, R. H. (2012) · Journal of Leukocyte Biology · doi:10.1189/jlb.0112033 · Cited by 51 · see citing works
de la Torre, R., Peña, E., Vilahur, G., Slevin, M., & Badimón, L. (2013) · Journal of Thrombosis and Haemostasis · doi:10.1111/jth.12415 · Cited by 44 · see citing works
The Long Pentraxin PTX3 Promotes Fibrocyte Differentiation
Pilling, D., Cox, N., Vakil, V., Verbeek, J. S., & Gomer, R. H. (2015) · PLoS ONE · doi:10.1371/journal.pone.0119709 · Cited by 44 · see citing works
“Therefore, the differential effect of SAP and PTX3 on fibrocyte differentiation may be due to the pentameric structure of SAP, compared to the decameric structure of PTX3, or the affinity of these pentraxins for FcγR [5,34,105,106].”
BackgroundSerum Amyloid P Component as a Biomarker in Mild Cognitive Impairment and Alzheimer’s Disease
Verwey, N., Schuitemaker, A., van der Flier, W. M., Mulder, S., Mulder, C., Hack, C., Scheltens, P., Blankenstein, M., & Veerhuis, R. (2008) · Dementia and Geriatric Cognitive Disorders · doi:10.1159/000178756 · Cited by 43 · see citing works
“Human SAP is a glycoprotein that exists as a pentameric ring-like structure of noncovalently bound subunits in serum [”
BackgroundDifferentiation of Circulating Monocytes into Fibroblast-Like Cells
Pilling, D., & Gomer, R. (2012) · Methods in molecular biology · doi:10.1007/978-1-61779-943-3_16 · Cited by 43 · see citing works
“Nevertheless, in plasma and in solutions containing at least 10 mg/ml albumin SAP remains a pentamer, even in the presence of 2 mM calcium (48, 49).”
BackgroundSerum amyloid P component inhibits influenza A virus infections: in vitro and in vivo studies.
Horváth, A., Andersen, I., Junker, K., Fogh-Schultz, B. L., Nielsen, E. H., Gizurarson, S., Andersen, O., Karman, J., Rajnavölgyi, É., Erdei, A., et al. (2001) · Antiviral Research · doi:10.1016/s0166-3542(01)00158-9 · Cited by 42 · see citing works
Combined Biomarkers Predict Acute Mortality Among Critically Ill Patients with Suspected Sepsis
Kelly, B. J., Lautenbach, E., Nachamkin, I., Coffin, S., Gerber, J., Fuchs, B., Garrigan, C., Han, X.-Y., Bilker, W., Wise, J., et al. (2018) · Critical Care Medicine · doi:10.1097/ccm.0000000000003137 · Cited by 37 · see citing works
Mikolajek, H., Kolstoe, S., Pye, V. E., Mangione, P., Pepys, M., & Wood, S. P. (2011) · Journal of Molecular Recognition · doi:10.1002/jmr.1090 · Cited by 36 · see citing works
“…CRP is readily determined by conventional equilibrium dialysis (Gotschlich and Edelman, 1967) but this is not possible with human SAP because the isolated protein aggressively aggregates at physiological ionic strength in the presence of calcium ions (Baltz et al., 1982a; Hutchinson et al., 2000).”
BackgroundSelf-citationNaCl Potentiates Human Fibrocyte Differentiation
Cox, N., Pilling, D., & Gomer, R. H. (2012) · PLoS ONE · doi:10.1371/journal.pone.0045674 · Cited by 28 · see citing works
“Serum Amyloid P (SAP), a pentameric protein from the pentraxin family of proteins, interacts with Fc receptors on monocytes to inhibit fibrocyte differentiation [13–16].”
BackgroundIsolation of two C-reactive protein homologues from cod (Gadus morhua L.) serum.
Gísladóttir, B., Gudmundsdóttir, S., Brown, L., Jónsson, Z., & Magnadóttir, B. (2009) · Fish and Shellfish Immunology · doi:10.1016/j.fsi.2008.03.015 · Cited by 35
“SAP) require Ca2þ and a stabilizing ligand like albumin to form a stable pentamer [10].”
BackgroundThompson, D., Pepys, M., Tickle, I., & Wood, S. (2002) · Journal of Molecular Biology · doi:10.1016/s0022-2836(02)00514-4 · Cited by 35 · see citing works
Self-citationAquilina, J., & Robinson, C. V. (2003) · Biochemical Journal · doi:10.1042/bj20030541 · Cited by 33 · see citing works
SAP Suppresses the Development of Experimental Autoimmune Encephalomyelitis in C57BL6 Mice
Ji, Z., Ke, Z.-J., & Geng, J. (2011) · Immunology and Cell Biology · doi:10.1038/icb.2011.51 · Cited by 29 · see citing works
Mulder, S., Hack, C., van der Flier, W. M., Scheltens, P., Blankenstein, M., & Veerhuis, R. (2011) · Journal of Alzheimer's Disease · doi:10.3233/jad-2010-100888 · Cited by 29 · see citing works
“pentameric disk [2,3].”
InfluentialLigand-assisted Aggregation of Proteins
Ho, J., Kitov, P., Paszkiewicz, E., Sadowska, J., Bundle, D., & Ng, K. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m504403200 · Cited by 29 · see citing works
Pentraxins, Anti-pentraxin Antibodies, and Atherosclerosis
Bassi, N., Zampieri, S., Ghirardello, A., Tonon, M., Zen, M., Cozzi, F., & Doria, A. (2009) · Clinical reviews in allergy and immunology · doi:10.1007/s12016-008-8098-6 · Cited by 28 · see citing works
“SAP is organized like a flat cyclic pentamer, formed by five noncovalently associated identical subunits of 25 kDa [65, 66] and its gene maps to chromosome 1 in close proximity to the CRP gene.”
BackgroundOzawa, D., Nomura, R., Mangione, P. P., Hasegawa, K., Okoshi, T., Porcari, R., Bellotti, V., & Naiki, H. (2016) · Scientific Reports · doi:10.1038/srep29077 · Cited by 25 · see citing works
“Interestingly, in the presence of Ca2+, CRP and SAP were less effective than in the absence of Ca2+ in preventing the aggregation of Aβ (1-40).”
BackgroundInfluentialHernaiz, M., Lebrun, L., Wu, Y., Sen, J. W., Linhardt, R., & Heegaard, N. (2002) · European Journal of Biochemistry · doi:10.1046/j.1432-1033.2002.02964.x · Cited by 27
Klotz, S. A., Sobonya, R. E., Lipke, P. N., & Garcia-Sherman, M. C. (2016) · Open Forum Infectious Diseases · doi:10.1093/ofid/ofw166 · Cited by 22 · see citing works
“Each protomer of SAP is a 25 kDa domain with a β-jelly roll fold, and the pentamer has a total Mr of 127 310 [8].”
BackgroundA serum amyloid P‐binding hydrogel speeds healing of partial thickness wounds in pigs
Gomer, R. H., Pilling, D., Kauvar, L. M., Ellsworth, S. L., Ronkainen, S. D., Roife, D., & Davis, S. C. (2009) · Wound Repair and Regeneration · doi:10.1111/j.1524-475x.2009.00482.x · Cited by 20 · see citing works
Rostagno, A., Lashley, T., Ng, D., Meyerson, J., Braendgaard, H., Plant, G., Bojsen-Møller, M., Holton, J., Frangione, B., Révész, T., et al. (2007) · Journal of Neurological Sciences · doi:10.1016/j.jns.2007.01.050 · Cited by 22 · see citing works
“Isolated SAP in solution and in physiological buffers is a stable decamer composed of two pentamers interacting phase to phase [3].”
BackgroundSerum Amyloid P Component (SAP) Interactome in Human Plasma Containing Physiological Calcium Levels.
Poulsen, E., Pedersen, K. W., Marzeda, A. M., & Enghild, J. (2017) · Biochemistry · doi:10.1021/acs.biochem.6b01027 · Cited by 18
“presence of physiological albumin concentrations.((19)) The biological functions of SAP are still unclear, but”
BackgroundKolstoe, S., & Wood, S. (2010) · Biochemical Society Transactions · doi:10.1042/bst0380466 · Cited by 18
Bergsma, D., Chen, S.-M., Buchweitz, J., Gerszten, R., & Haab, B. (2009) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m900418-mcp200 · Cited by 18
“partner in the circulation (27, 28), although other studies on”
BackgroundResultSerum amyloid P secreted by bone marrow adipocytes drives skeletal amyloidosis
Kumar, S., Song, K., Wang, J., Baghel, M. S., Zeng, Y., Shen, K., Zheng, J., Crane, J., Demehri, S., Gao, P., et al. (2025) · Nature Aging · doi:10.1038/s43587-025-00924-z · Cited by 16 · see citing works
Malicek, D., Wittig, I., Luger, S., & Foerch, C. (2021) · Frontiers in Neurology · doi:10.3389/fneur.2021.713124 · Cited by 16 · see citing works
“APCS binds to apoptotic cells, is involved in chromatin degradation, and acts toxic to cerebral neurons (125, 126).”
BackgroundHeegaard, N., He, X.-Y., & Blomberg, L. (2006) · Electrophoresis · doi:10.1002/elps.200600005 · Cited by 16
Shirai, K., Hikita, H., Sakane, S., Narumi, R., Adachi, J., Doi, A., Tanaka, S., Tahata, Y., Yamada, R., Kodama, T., et al. (2022) · PLoS ONE · doi:10.1371/journal.pone.0271020 · Cited by 15 · see citing works
“SAP is synthesized by the liver and circulates in the blood as a stable pentamer [25].”
BackgroundAn Improved Method for the Sensitive Detection of Shiga Toxin 2 in Human Serum
He, X., Ardissino, G., Patfield, S., Cheng, L. W., Silva, C. J., & Brigotti, M. (2018) · Toxins · doi:10.3390/toxins10020059 · Cited by 15
“Isolated HuSAP, however, forms stable decamers in the absence of calcium and low molecular weight ligands, and rapidly auto aggregates in the presence of calcium and absence of low molecular weight ligands [23].”
BackgroundInteraction of serum amyloid P component with hexanoyl bis(d-proline) (CPHPC)
Kolstoe, S., Jenvey, M. C., Purvis, A., Light, M., Thompson, D., Hughes, P., Pepys, M., & Wood, S. (2014) · Acta Crystallographica Section D: Biological Crystallography · doi:10.1107/s1399004714013455 · Cited by 14
“A high calcium chloride concentration was used to prevent the calcium-dependent auto-aggregation of isolated human SAP which occurs at physiological ionic strength (Hutchinson et al., 2000).”
MethodSelf-citationCombined analysis of serum SAP and PRSS2 for the differential diagnosis of CD and UC.
Wang, W., Wu, L.-X., Wu, X., Li, K., Li, T.-M., Xu, B., & Liu, W. (2020) · Clinica chimica acta; international journal of clinical chemistry · doi:10.1016/j.cca.2020.12.014 · Cited by 13 · see citing works
Binding of human serum amyloid P componentto L‐selectin
Stibenz, D., Gräfe, M., Debus, N., Hasbach, M., Bahr, I., Graf, K., Fleck, E., Thanabalasingam, U., & Bührer, C. (2006) · European Journal of Immunology · doi:10.1002/eji.200425360 · Cited by 13 · see citing works
Jin, Y., Bu, S., Zhang, J., Yuan, Q., Manabe, T., & Tan, W. (2014) · Electrophoresis · doi:10.1002/elps.201300628 · Cited by 12 · see citing works
Sen, J. W., Recke, C., Rahbek, L., Skogstrand, K., & Heegaard, N. (2002) · Scandinavian Journal of Immunology · doi:10.1046/j.1365-3083.2002.01178.x · Cited by 12 · see citing works
Yang, J., Zhou, J.-J., Zhou, J., Wang, H., Sun, Z., Zhu, X.-Q., He, Y., Wong, A., Liu, F., & Wang, G. (2021) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2021.12.051 · Cited by 10 · see citing works
Sen, J. W., & Heegaard, N. (2002) · Scandinavian Journal of Immunology · doi:10.1046/j.1365-3083.2002.01109.x · Cited by 8
Exploring Intrinsic Disorder in Human Synucleins and Associated Proteins
Venati, S. R., & Uversky, V. N. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25158399 · Cited by 6 · see citing works
Colston, J. M., Yori, P. P., Moulton, L. H., Olórtegui, M. P., Kosek, P. S., Trigoso, D. R., Salas, M. S., Schiaffino, F., François, R., Fardus‐Reid, F., et al. (2019) · PLoS neglected tropical diseases · doi:10.1371/journal.pntd.0007851 · Cited by 6 · see citing works
“The fact that CRP is inversely related to Fetuin-A [52] and, like SAP, is a calcium-dependent ligand binding plasma protein [46] may mean that the presence of the latter protein in the final model fully accounted for any effect of CRP.”
BackgroundWang, Y., Chen, W., Ding, S., Wang, W., & Wang, C. (2023) · Developmental & Comparative Immunology · doi:10.1016/j.dci.2023.105064 · Cited by 7 · see citing works
Dorta-Estremera, S. M. (2015) · Journal of Clinical & Cellular Immunology · doi:10.4172/2155-9899.1000332 · Cited by 4 · see citing works
“Acidic conditions can promote structural misfolding of proteins; therefore, acidic conditions can facilitate the formation of APs in vitro [43,44].”
BackgroundWei, L.-M., Wang, Y., Lin, L., Zhang, L., Shi, Y., Xiang, P., Cao, S., Shen, M., & Yang, P.-Y. (2018) · RSC Advances · doi:10.1039/c7ra12956d · Cited by 4
Amilina: del estudio molecular a las acciones fisiológicas
Rojas, I., & Novials, A. (2001) · Endocrinología y Nutrición · doi:10.1016/s1575-0922(01)74399-9 · Cited by 4 · see citing works
Local Pentraxin-2 Deficit Is a Feature of Intestinal Fibrosis in Crohn’s Disease
Levitte, S., Peale, F., Jhun, I., McBride, J., & Neighbors, M. (2023) · Digestive Diseases and Sciences · doi:10.1007/s10620-023-07909-1 · Cited by 2 · see citing works
“PTX-2 is constitutively expressed in the liver and secreted into the serum, but its localization within the gastrointestinal tract remains undescribed [11].”
BackgroundMa, J.-H., Liu, Q., & White, J. R. (2021) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2021.101136 · Cited by 1 · see citing works
“SAP as the pentamer has been shown to exist in serum or in vitro in the presence of physiological albumin concentrations (29).”
BackgroundComparative Study on Metabolic Regulation of SAP Deletion in Normal Mice and Atherosclerotic Mice
Zhu, Y., Xie, S., Shu, H., Lu, Y., Guo, J., Li, Q., Zhang, Y.-L., & Yang, Y.-X. (2025) · Health and Metabolism · doi:10.53941/hm.2025.100020
“In addition, it was reported that SAP can interact with pathogens and cell debris to activate the complement pathway and promote macrophages and neutrophils to clear the pathogens and cell debris [6].”
Dwari, D. (2024) · Social Science Research Network · doi:10.2139/ssrn.4873931
“Generally, there are five folded subunits form a ring having a diameter of 20A and 35A depth in the center, which contains a positive charge cluster Ionic interactions stabilize the decamer, allowing access to the incurvate facing side of each pentamer [34].”
Fibrocytes and Pulmonary Vascular Remodeling: The Good, the Bad, and the Progenitors
Colvin, K. L., Lohani, O., & Yeager, M. E. (2015) · Stem cell biology and regenerative medicine · doi:10.1007/978-3-319-16232-4_14
- Authors
- Hutchinson, W. L., Hohenester, E., & Pepys, M. B.
- Affiliations
- Hammersmith Hospital (GB)
- University of London (GB)
- The Royal Free Hospital (GB)
- Venue
- Molecular Medicine
- Published
- 2000-06
- Volume
- 6
- Issue
- 6
- Pages
- 482-493
- ISSN
- 1076-1551 (ISSN-L)
- 1528-3658
- PMC
- PMC1949963
- OpenAlex
- W1677800424
- Cited by
- 66
- References
- 51
- Citations by year
- 2025: 4 · 2024: 1 · 2023: 2 · 2022: 1 · 2021: 3 · 2020: 2 · 2019: 1 · 2018: 5 · 2016: 3 · 2015: 4 · 2014: 4 · 2013: 2 · 2012: 3
- FWCI
- 1.18
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Molecular Medicine (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- Medical Research Council
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Biomarkers in Disease Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein purification and stability
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › S100 Proteins and Annexins
- Keywords
- serum amyloid P component, oligomeric assembly, pentamer, decamer, self-aggregation, calcium dependence, human serum albumin, C-reactive protein, amyloid deposits, molecular weight determination
- MeSH terms
- Serum Amyloid P-Component, C-Reactive Protein, Centrifugation, Density Gradient, Chromatography, Gel, Humans, Ligands, Molecular Weight, Serum Albumin, Protein Structure, Quaternary, Macromolecular Substances
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