Crystal Structure of Human Cyclophilin A Bound to the Amino-Terminal Domain of HIV-1 Capsid

Gamble, Theresa R; Vajdos, Felix F; Yoo, Sanghee; Worthylake, David K; Houseweart, Megan; Sundquist, Wesley I; Hill, Christopher P

doi:10.1016/s0092-8674(00)81823-1

Cited by 710HIV Research and TreatmentSignaling Pathways in DiseaseHIV/AIDS drug development and treatment

Crystal Structure of Human Cyclophilin A Bound to the Amino-Terminal Domain of HIV-1 Capsid

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Gamble, Theresa R, Vajdos, Felix F, Yoo, Sanghee, Worthylake, David K, Houseweart, Megan, Sundquist, Wesley I, Hill, Christopher P·1996·Cell

DOI 10.1016/s0092-8674(00)81823-1

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Abstract

The HIV-1 capsid protein forms the conical core structure at the center of the mature virion. Capsid also binds the human peptidyl prolyl isomerase, cyclophilin A, thereby packaging the enzyme into the virion. Cyclophilin A subsequently performs an essential function in HIV-1 replication, possibly helping to disassemble the capsid core upon infection. We report the 2.36 A crystal structure of the N-terminal domain of HIV-1 capsid (residues 1-151) in complex with human cyclophilin A. A single exposed capsid loop (residues 85-93) binds in the enzyme's active site, and Pro-90 adopts an unprecedented trans conformation. The structure suggests how cyclophilin A can act as a sequence-specific binding protein and a nonspecific prolyl isomerase. In the crystal lattice, capsid molecules assemble into continuous planar strips. Side by side association of these strips may allow capsid to form the surface of the viral core. Cyclophilin A could then function by weakening the association between capsid strips, thereby promoting disassembly of the viral core.

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A beta-hairpin is formed by the N-terminal residues in mature-like CA, stabilized by a salt bridge between the N-terminal proline and a conserved aspartate in helix 3.
“A beta-hairpin is formed by the N-terminal residues in mature-like CA, stabilized by a salt bridge between the N-terminal proline and a conserved aspartate in helix 3”
From Retrovirus maturation-an extraordinary structural transformation (2016) · cites this paper as [72]

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Background
Solution Conformation of a Cyclophilin-Bound Proline Isomerase Substrate
Kakalis, L. T., & Armitage, I. M. (1994) · Biochemistry · doi:10.1021/bi00172a028 · Cited by 17 · cited 1× · see citing works
“…and hydrogen bonding to the amide nitrogen of CA Pro-90 (Zhao and Ke, 1996a), although the Arg-55 Nh2 to Pro-Walkinshaw, 1992; Ke et al., 1993; Kakalis and Armitage, 1994; Schutkowski et al., 1995; Zhao and Ke, 1996a; 90 N distance for both of the CA151/CypA complexes in the asymmetric unit…”
Background
Mode of action of SDZ NIM 811, a non-immunosuppressive Cyclosporin A analog with activity against human immunodeficiency virus type 1 (HIV-1)
Rosenwirth, B., Billich, A., Steinkasserer, A., Hammerschmid, F., & Peichl, P. (1995) · Antiviral Research · doi:10.1016/0166-3542(95)94702-4 · Cited by 3 · see citing works

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Sorted by citations

The atomic structure of protein-protein recognition sites 1 1Edited by A. R. Fersht
Conte, L. L., Chothia, C., & Janin, J. (1999) · Journal of Molecular Biology · doi:10.1006/jmbi.1998.2439 · Cited by 1,967 · see citing works
“…A-Fc fragment 2.8 1300 2 Deisenhofer (1981) 1igc Protein G-Fab MOPC21 2.6 1350 14 Derrick & Wigley (1994) 1ak4 Cyclophilin-HIV capsid 2.4 1170 8 3 Gamble et al. (1996) 1efn Fyn SH3 domain-HIV Nef 2.5 1260 7 Lee et al. (1996) 1atn Actin-DNase I 2.8 1780 8 Kabsch et al. (1990) 2btf Actin-profilin…”
Influential
Absence of S6K1 protects against age- and diet-induced obesity while enhancing insulin sensitivity
Um, S. H., Frigerio, F., Watanabe, M., Picard, F., Joaquin, M., Sticker, M., Fumagalli, S., Allegrini, P. R., Kozma, S. C., Auwerx, J., et al. (2004) · Nature · doi:10.1038/nature02866 · Cited by 1,677 · see citing works
Cis−Trans Isomerization of Organic Molecules and Biomolecules: Implications and Applications
Dugave, C., & Demange, L. (2003) · Chemical Reviews · doi:10.1021/cr0104375 · Cited by 1,033 · see citing works
HIV-1: Fifteen Proteins and an RNA
Frankel, A. D., & Young, J. A. T. (1998) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.67.1.1 · Cited by 913 · see citing works
Host-directed therapies for bacterial and viral infections
Kaufmann, S. H. E., Dorhoi, A., Hotchkiss, R. S., & Bartenschlager, R. F. W. (2017) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2017.162 · Cited by 847 · see citing works
Enzyme Dynamics During Catalysis
Eisenmesser, E. Z., Bosco, D. A., Akke, M., & Kern, D. (2002) · Science · doi:10.1126/science.1066176 · Cited by 732 · see citing works
HIV-1 Gag proteins: diverse functions in the virus life cycle
Freed, E. O. (1998) · Virology · doi:10.1006/viro.1998.9398 · Cited by 717 · see citing works
“Mutational analysis indicated that the domain responsible for CypA incorporation resided in the vicinity of Pro 90 (Franke et al., 1994b); this conclusion was confirmed by the cocrystallization of CA with CypA (Gamble et al., 1996).”
BackgroundMethodInfluential
Structural and Functional Analysis of the Mitotic Rotamase Pin1 Suggests Substrate Recognition Is Phosphorylation Dependent
Ranganathan, R., Lu, K. P., Hunter, T. R., & Noel, J. P. (1997) · Cell · doi:10.1016/s0092-8674(00)80273-1 · Cited by 703 · see citing works
“In light of the multivalent nature of the bound sulfate ion, we propose that Pin1 will C-terminal to these residues (Gamble et al., 1996). preferentially catalyze isomerization of peptide bonds involving a minimal segment consisting of a P.Ser or P.Thr residue N-terminal to proline.”
Background
TRIM family proteins: retroviral restriction and antiviral defence
Nisole, S., Stoye, J. P., & Saïb, A. (2005) · Nature Reviews Microbiology · doi:10.1038/nrmicro1248 · Cited by 761 · see citing works
HIV-1 assembly, release and maturation
Freed, E. O. (2015) · Nature Reviews Microbiology · doi:10.1038/nrmicro3490 · Cited by 654 · see citing works
“Subsequent structural studies demonstrated that MA interacts directly with the negatively charged inositol headgroup of PtdIns(4,5)P2 (REFS 11,12).”
BackgroundInfluential
Peptidyl-prolyl cis-trans isomerases, a superfamily of ubiquitous folding catalysts
G�thel, S. F., & Marahiel, M. A. (1999) · Cellular and Molecular Life Sciences · doi:10.1007/s000180050299 · Cited by 649 · see citing works
Structure of the carboxyl-terminal dimerization domain of the HIV-1 capsid protein
Gamble, T. R., Yoo, S., Vajdos, F. F., von Schwedler, U. K., Worthylake, D. K., Wang, H., McCutcheon, J. P., Sundquist, W. I., & Hill, C. P. (1997) · Science · doi:10.1126/science.278.5339.849 · Cited by 598 · see citing works
Self-citation
Formation of a Human Immunodeficiency Virus Type 1 Core of Optimal Stability Is Crucial for Viral Replication
Forshey, B. M., von Schwedler, U. K., Sundquist, W. I., & Aiken, C. (2002) · Journal of Virology · doi:10.1128/jvi.76.11.5667-5677.2002 · Cited by 514 · see citing works
“Structural studies have revealed that CA consists of two distinct, globular domains connected by a flexible linker: an amino-terminal domain, composed of seven -helices and a -hairpin, and a carboxyl-terminal domain, composed of a 310 helix and four -helices (15, 16, 18, 29, 31).”
BackgroundSelf-citation
The structural biology of HIV assembly
Ganser‐Pornillos, B. K., Yeager, M. J., & Sundquist, W. I. (2008) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2008.02.001 · Cited by 500 · see citing works
Self-citation
HIV and SIV CTL escape: implications for vaccine design
Goulder, P., & Watkins, D. I. (2004) · Nature reviews. Immunology · doi:10.1038/nri1417 · Cited by 494 · see citing works
“Modelling of these mutations supports this idea, because R264 seems to occupy a crucial position in the capsid protein, being situated centrally in helix-7 and seemingly directly mediating the dimerization of p24 Gag (the capsid protein”
Background
Structural biology of HIV 1 1Edited by P. E. Wright
Turner, B. G., & Summers, M. F. (1999) · Journal of Molecular Biology · doi:10.1006/jmbi.1998.2354 · Cited by 470 · see citing works
“Details of the intermolecular interactions have been obtained from X-ray structural studies of the CA core-CypA complex (Gamble et al., 1996).”
BackgroundMethodInfluential
Image reconstructions of helical assemblies of the HIV-1 CA protein
Li, S., Hill, C. P., Sundquist, W. I., & Finch, J. T. (2000) · Nature · doi:10.1038/35030177 · Cited by 500 · see citing works
Self-citation
Assessing the performance of the MM/PBSA and MM/GBSA methods. 6. Capability to predict protein–protein binding free energies and re-rank binding poses generated by protein–protein docking
Chen, F., Liu, H., Sun, H., Pan, P., Li, Y., Li, D., & Hou, T. (2016) · Physical Chemistry Chemical Physics · doi:10.1039/c6cp03670h · Cited by 463 · see citing works
Efficient docking of peptides to proteins without prior knowledge of the binding site
Hetényi, C., & van der Spoel, D. (2002) · Protein Science · doi:10.1110/ps.0202302 · Cited by 454 · see citing works
“The latter finding hints at the possibility of a combination of blind docking with fragment docking ( Friedman et al. 1994 ) and to studies of proteinprotein interactions.”
Background
Host Cell Factors in HIV Replication: Meta-Analysis of Genome-Wide Studies
Bushman, F. D., Malani, N., Fernandes, J. D., D’Orso, I., Cagney, G., Diamond, T. L., Zhou, H., Hazuda, D. J., Espeseth, A. S., König, R., et al. (2009) · PLoS Pathogens · doi:10.1371/journal.ppat.1000437 · Cited by 452 · see citing works
“. Several genes known to encode products important for HIV replication were identified in the initial screen of Konig et al., which yielded 4,019 candidates, but were not further validated in the filtered data set of 293 proteins. These included Sp1, a transcription factor known to bind the HIV LTR; the HIV Gag bindin…”
Background
Clustered Mutations in HIV-1 Gag Are Consistently Required for Escape from Hla-B27–Restricted Cytotoxic T Lymphocyte Responses
Kelleher, A. D., Long, C., Holmes, E. C., Allen, R. L., Wilson, J., Conlon, C. P., Workman, C., Shaunak, S., Olson, K., Goulder, P., et al. (2001) · The Journal of Experimental Medicine · doi:10.1084/jem.193.3.375 · Cited by 448 · see citing works
“It may also indicate that in vivo the mutation is only tolerable in subtype B viruses, all of which on the database have E260, when E260D and R264G mutations occur in the presence of L268.”
BackgroundInfluential
Fitness Cost of Escape Mutations in p24 Gag in Association with Control of Human Immunodeficiency Virus Type 1
Martínez‐Picado, J., Prado, J. G., Fry, E. E., Pfafferott, K. J., Leslie, A. J., Chetty, S., Thobakgale, C., Honeyborne, I., Crawford, H., Matthews, P. C., et al. (2006) · Journal of Virology · doi:10.1128/jvi.80.7.3617-3623.2006 · Cited by 447 · see citing works
“As with other epitopes associated with successful HIV/SIV control (4, 13, 14, 19), the capsid protein is a promising target for effective CTL, perhaps because of selection pressure against single escape mutations arising in the absence of linked compensatory changes.”
Background
HIV-1 capsid: the multifaceted key player in HIV-1 infection
Campbell, E. M., & Hope, T. J. (2015) · Nature Reviews Microbiology · doi:10.1038/nrmicro3503 · Cited by 430 · see citing works
The structural biology of HIV-1: mechanistic and therapeutic insights
Engelman, A., & Cherepanov, P. (2012) · Nature Reviews Microbiology · doi:10.1038/nrmicro2747 · Cited by 426 · see citing works
“CA, which comprises independently folded N-terminal and C-terminal domains (NTD and CTD, respectively) connected by a flexible linke”
Background
Functional Surfaces of the Human Immunodeficiency Virus Type 1 Capsid Protein
von Schwedler, U. K., Stray, K. M., Garrus, J. E., & Sundquist, W. I. (2003) · Journal of Virology · doi:10.1128/jvi.77.9.5439-5450.2003 · Cited by 421 · see citing works
“HIV-1 (4, 34, 38, 64), equine infectious anemia virus (47),”
BackgroundSelf-citation
Structures of the CCR5 N Terminus and of a Tyrosine-Sulfated Antibody with HIV-1 gp120 and CD4
Huang, C.-C., Lam, S. N., Acharya, P., Tang, M., Xiang, S.-H., Shahzad‐ul‐Hussan, S., Stanfield, R. L., Robinson, J. E., Sodroski, J., Wilson, I. A., et al. (2007) · Science · doi:10.1126/science.1145373 · Cited by 416 · see citing works
From SARS to MERS: 10 years of research on highly pathogenic human coronaviruses
Hilgenfeld, R., & Peiris, M. J. S. (2013) · Antiviral Research · doi:10.1016/j.antiviral.2013.08.015 · Cited by 347 · see citing works
“The latter binds to cyclophilin A (CypA), a peptidyl prolyl cis/trans isomerase of the host cell, which is incorporated into the HIV particle (Gamble et al., 1996).”
Background
Proteolytic refolding of the HIV‐1 capsid protein amino‐terminus facilitates viral core assembly
von Schwedler, U. K., Stemmler, T. L., Klishko, V. Y., Li, S., Albertine, K. H., Davis, D. R., & Sundquist, W. I. (1998) · The EMBO Journal · doi:10.1093/emboj/17.6.1555 · Cited by 337 · see citing works
“Guided by the crystal structure of CA151 (Gamble et al., 1996), we designed five point mutations that were expected to disrupt the amino-terminal capsid interface, but minimize other structural perturbations.”
BackgroundMethodInfluentialSelf-citation
The Interferon-Inducible MxB Protein Inhibits HIV-1 Infection
Liu, Z., Pan, Q., Ding, S., Qian, J., Xu, F., Zhou, J., Cen, S., Guo, F., & Liang, C. (2013) · Cell Host & Microbe · doi:10.1016/j.chom.2013.08.015 · Cited by 336 · see citing works
Sequential Steps in Human Immunodeficiency Virus Particle Maturation Revealed by Alterations of Individual Gag Polyprotein Cleavage Sites
Wiegers, K., Rutter, G., Kottler, H., Tessmer, U., Hohenberg, H., & Kräusslich, H.-G. (1998) · Journal of Virology · doi:10.1128/jvi.72.4.2846-2854.1998 · Cited by 336 · see citing works
“Structure determination of a fragment of HIV-1 CA (18, 41) revealed an N-terminal b-hairpin stabilized by hydrogen bonding involving the amino group of proline 1 of CA, which is only exposed after proteolytic cleavage (13, 18).”
Active Site Residues of Cyclophilin A Are Crucial for Its Signaling Activity via CD147
Yurchenko, V., Zybarth, G., O’Connor, M. J., Dai, W. W., Franchin, G., Tang, H., Guo, H., Hung, H., Toole, B. P., Gallay, P. A., et al. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m201593200 · Cited by 334 · see citing works
Structure of Full-Length HIV-1 CA: A Model for the Mature Capsid Lattice
Ganser-Pornillos, B. K., Cheng, A., & Yeager, M. (2007) · Cell · doi:10.1016/j.cell.2007.08.018 · Cited by 321 · see citing works
“…the HIV-1 CA NTD is shaped as an arrowhead, with seven a helices (numbered 1–7) and an amino-terminal b-hairpin (Berthet-Colominas et al., 1999; Gamble et al., 1996; Gitti et al., 1996), while the CTD is more globular, with a single-turn 3 10 -helix and four short a helices (numbered 8–11)…”
Escape from the Dominant HLA-B27-Restricted Cytotoxic T-Lymphocyte Response in Gag Is Associated with a Dramatic Reduction in Human Immunodeficiency Virus Type 1 Replication
Schneidewind, A., Brockman, M. A., Yang, R., Adam, R. I., Li, B., Gall, S. L., Rinaldo, C. R., Craggs, S. L., Allgaier, R. L., Power, K. A., et al. (2007) · Journal of Virology · doi:10.1128/jvi.01543-07 · Cited by 315 · see citing works
“The underlying mechanism of this dependency on CypA remains unclear, although it has been suggested to be related to the regulation of capsid stability (33, 37), uncoating (35), or impairment of recognition of capsid by host restriction factors (71).”
BackgroundInfluential
Assembly Properties of the Human Immunodeficiency Virus Type 1 CA Protein
Ganser-Pornillos, B. K., von Schwedler, U. K., Stray, K. M., Aiken, C., & Sundquist, W. I. (2004) · Journal of Virology · doi:10.1128/jvi.78.5.2545-2552.2004 · Cited by 302 · see citing works
“important for infectivity and assembly (18, 52, 53, 56).”
BackgroundSelf-citation
Nucleoporin NUP153 Phenylalanine-Glycine Motifs Engage a Common Binding Pocket within the HIV-1 Capsid Protein to Mediate Lentiviral Infectivity
Matreyek, K. A., Yücel, S. S., Li, X., & Engelman, A. (2013) · PLoS Pathogens · doi:10.1371/journal.ppat.1003693 · Cited by 280 · see citing works
“…A (CypA) and the NUP358 cyclophilin homologous domain (CHD), both of which bind the cyclophilin binding loop protruding from the top of the CA NTD [39,40], or cleavage and polyadenylation specific factor 6 (CPSF6), which binds a hydrophobic pocket [41] located between a -helices 3 and 4 within…”
Background
HIV Capsid is a Tractable Target for Small Molecule Therapeutic Intervention
Blair, W. S., Pickford, C., Irving, S. L., Brown, D. G., Anderson, M. D., Bazin, R., Cao, J. Q., Ciaramella, G., Isaacson, J., Jackson, L., et al. (2010) · PLoS Pathogens · doi:10.1371/journal.ppat.1001220 · Cited by 291 · see citing works
HLA-B57/B*5801 Human Immunodeficiency Virus Type 1 Elite Controllers Select for Rare Gag Variants Associated with Reduced Viral Replication Capacity and Strong Cytotoxic T-Lymphotye Recognition
Miura, T., Brockman, M. A., Schneidewind, A., Lobritz, M. A., Pereyra, F., Rathod, A., Block, B. L., Brumme, Z. L., Brumme, C. J., Baker, B. M., et al. (2008) · Journal of Virology · doi:10.1128/jvi.02265-08 · Cited by 294 · see citing works
“binding loop, which is just upstream of TW10 (18, 19), were”
Background
In vitro assembly properties of human immunodeficiency virus type 1 Gag protein lacking the p6 domain
Campbell, S., & Rein, A. (1999) · Journal of Virology · doi:10.1128/jvi.73.3.2270-2279.1999 · Cited by 293 · see citing works
A Knowledge-Based Energy Function for Protein−Ligand, Protein−Protein, and Protein−DNA Complexes
Zhang, C., Liu, S., Zhu, Q., & Zhou, Y. (2005) · Journal of Medicinal Chemistry · doi:10.1021/jm049314d · Cited by 287 · see citing works
Cyclophilin A regulates HIV‐1 infectivity, as demonstrated by gene targeting in human T cells
Braaten, D. C., & Luban, J. (2001) · The EMBO Journal · doi:10.1093/emboj/20.6.1300 · Cited by 275 · see citing works
Regulation of the tyrosine kinase Itk by the peptidyl-prolyl isomerase cyclophilin A
Brazin, K. N., Mallis, R. J., Fulton, D. B., & Andreotti, A. H. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.042529199 · Cited by 275 · see citing works
Essential Role of Cyclophilin A for Hepatitis C Virus Replication and Virus Production and Possible Link to Polyprotein Cleavage Kinetics
Kaul, A., Stauffer, S., Berger, C., Pertel, T., Schmitt, J., Kallis, S., Zayas, M., Lohmann, V., Luban, J., & Bartenschlager, R. F. W. (2009) · PLoS Pathogens · doi:10.1371/journal.ppat.1000546 · Cited by 267 · see citing works
TRIM5 Suppresses Cross-Species Transmission of a Primate Immunodeficiency Virus and Selects for Emergence of Resistant Variants in the New Species
Kirmaier, A., Wu, F., Newman, R. M., Hall, L. R., Morgan, J. S., O’Connor, S. L., Marx, P. A., Meythaler, M., Goldstein, S. C., Buckler-White, A. J., et al. (2010) · PLoS Biology · doi:10.1371/journal.pbio.1000462 · Cited by 265 · see citing works
“. TRIM5CypA restriction of lentiviral infection involves specific binding to a peptide loop between helices 4 and 5 of the viral CA (also the binding site for cellular CypA)”
Background
Molecular recognition in the HIV-1 capsid/cyclophilin A complex 1 1Edited by J. A. Wells
Yoo, S., Myszka, D. G., Yeh, C.-Y., McMurray, M., Hill, C. P., & Sundquist, W. I. (1997) · Journal of Molecular Biology · doi:10.1006/jmbi.1997.1051 · Cited by 259 · see citing works
“Similarly, our recent CA 151 /CypA co-crystal structure revealed that capsid residues 85 to 93 make a series of favorable contacts in the CypA active site, with no other signi®cant CypA- CA or CypA-CypA interaction (Gamble et al., 1996).”
BackgroundMethodInfluentialSelf-citation
Escape and Compensation from Early HLA-B57-Mediated Cytotoxic T-Lymphocyte Pressure on Human Immunodeficiency Virus Type 1 Gag Alter Capsid Interactions with Cyclophilin A
Brockman, M. A., Schneidewind, A., Lahaie, M. P., Schmidt, A. G., Miura, T., DeSouza, I., Ryvkin, F., Derdeyn, C. A., Allen, S. A., Hunter, E., et al. (2007) · Journal of Virology · doi:10.1128/jvi.01369-07 · Cited by 261 · see citing works
“Upon binding to CypA, alpha helices I, II, IV, and VI in the amino-terminal domain show significant movement (3, 31).”
Background
Structural Convergence between Cryo-EM and NMR Reveals Intersubunit Interactions Critical for HIV-1 Capsid Function
Byeon, I.-J. L., Meng, X., Jung, J., Zhao, G., Yang, R., Ahn, J., Shi, J., Concel, J., Aiken, C., Zhang, P., et al. (2009) · Cell · doi:10.1016/j.cell.2009.10.010 · Cited by 253 · see citing works
Hexagonal assembly of a restricting TRIM5α protein
Ganser‐Pornillos, B. K., Chandrasekaran, V., Pornillos, O., Sodroski, J., Sundquist, W. I., & Yeager, M. J. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1013426108 · Cited by 248 · see citing works
Self-citation
Cryo-electron microscopy reveals ordered domains in the immature HIV-1 particle
Fuller, S. D., Wilk, T., Gowen, B. E., Kräusslich, H., & Vogt, V. M. (1997) · Current Biology · doi:10.1016/s0960-9822(06)00331-9 · Cited by 246 · see citing works
A conformational switch controlling HIV‐1 morphogenesis
Gross, I., Hohenberg, H., Wilk, T., Wiegers, K. J., Grättinger, M., Müller, B., Fuller, S., & Kräusslich, H. (2000) · The EMBO Journal · doi:10.1093/emboj/19.1.103 · Cited by 241 · see citing works
“…on molecular modeling, the C-terminus of CA and adjacent SP1 residues have been proposed to form a continuous α-helix (Accola et al., 1998), while this region was disordered in the structures of CA determined to date (Gamble et al., 1996; Berthet-Colominas et al., 1999; Worthylake et al., 1999).”
Background
Structures of the HIV-1 capsid protein dimerization domain at 2.6 Å resolution
Worthylake, D. K., Wang, H., Yoo, S., Sundquist, W. I., & Hill, C. P. (1999) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444998007689 · Cited by 235 · see citing works
“The three-dimensional structure of the N-terminal domain of the HIV-1 capsid has also been determined in solution (Gitti et al., 1996) and in crystals as complexes with an Fab fragment (Momany et al., 1996) and cyclophilin A (Gamble et al., 1996).”
Self-citation
Insights into the catalytic mechanism of peptidyl prolyl cis/trans isomerases
FanghÃ¤nel, J. (2004) · Frontiers in bioscience · doi:10.2741/1494 · Cited by 232 · see citing works
HIV-1 uses dynamic capsid pores to import nucleotides and fuel encapsidated DNA synthesis
Jacques, D. A., McEwan, W. A., Hilditch, L., Price, A. J., Towers, G. J., & James, L. C. (2016) · Nature · doi:10.1038/nature19098 · Cited by 221 · see citing works
Cyclophilin A Is an Essential Cofactor for Hepatitis C Virus Infection and the Principal Mediator of Cyclosporine Resistance In Vitro
Yang, F., Robotham, J. M., Nelson, H. B., Irsigler, A., Kenworthy, R., & Tang, H. (2008) · Journal of Virology · doi:10.1128/jvi.02614-07 · Cited by 231 · see citing works
“The well-characterized crystal structure of the CyPA-CA complex (9, 41, 48) may provide relevant insight and guidance for further characterization of the CyPANS5B interface.”
Background
Catalysis of cis/trans isomerization in native HIV-1 capsid by human cyclophilin A
Bosco, D. A., Eisenmesser, E. Z., Pochapsky, S. S., Sundquist, W. I., & Kern, D. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.082100499 · Cited by 226 · see citing works
Self-citation
Specific inhibition of hepatitis C virus replication by cyclosporin A
Nakagawa, M., Sakamoto, N., Enomoto, N., Tanabe, Y., Kanazawa, N., Koyama, T., Kurosaki, M., Maekawa, S., Yamashiro, T., Chen, C.-H., et al. (2003) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2003.11.080 · Cited by 229 · see citing works
Target Cell Cyclophilin A Modulates Human Immunodeficiency Virus Type 1 Infectivity
Sokolskaja, E., Sayah, D. M., & Luban, J. (2004) · Journal of Virology · doi:10.1128/jvi.78.23.12800-12808.2004 · Cited by 218 · see citing works
“X-ray and nuclear magnetic resonance analysis of CypA in complex with various Gag fragments confirmed that these residues participate in direct protein-protein interactions (27, 40, 47, 51, 57).”
Background
Regulation of peptide bond cis/trans isomerization by enzyme catalysis and its implication in physiological processes
Fischer, G. S., & Aumüller, T. (2003) · Springer eBooks · doi:10.1007/s10254-003-0011-3 · Cited by 221 · see citing works
Antiviral Inhibition of the HIV-1 Capsid Protein
Tang, C., Loeliger, E., Kinde, I., Kyere, S., Mayo, K., Barklis, E., Sun, Y., Huang, M., & Summers, M. F. (2003) · Journal of Molecular Biology · doi:10.1016/s0022-2836(03)00289-4 · Cited by 218 · see citing works
Retrovirus Restriction Factors
Goff, S. P. (2004) · Molecular Cell · doi:10.1016/j.molcel.2004.12.001 · Cited by 215 · see citing works
Highly Purified Human Immunodeficiency Virus Type 1 Reveals a Virtual Absence of Vif in Virions
Dettenhofer, M., & Yu, X.-F. (1999) · Journal of Virology · doi:10.1128/jvi.73.2.1460-1467.1999 · Cited by 239 · see citing works
“Analysis of virions obtained from the peak fractions of an OptiPrep velocity gradient indicated that viral Gag proteins CAp24, MAp17, and NCp7/p6Gag contributed more than 80% of the total protein content (Fig.”
BackgroundInfluential
Immunophilins: for the love of proteins
Barik, S. (2006) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-006-6215-3 · Cited by 210 · see citing works
Structure of the N-terminal 283-residue fragment of the immature HIV-1 Gag polyprotein
Tang, C., Ndassa, Y., & Summers, M. F. (2002) · Nature Structural Biology · doi:10.1038/nsb806 · Cited by 205 · see citing works
“The mature HIV-1 CA protein consists of the N-terminal 'core' (CA N ) and C-terminal dimerization (CA C ) domains, which are folded independently and connected by a flexible linke”
Background
Enzymes: An integrated view of structure, dynamics and function
Agarwal, P. K. (2006) · Microbial Cell Factories · doi:10.1186/1475-2859-5-2 · Cited by 204 · see citing works
“The proteinprotein complex between CypA and CA has been the subject of many experimental studies [16,34-37].”
Background
Early steps of retrovirus replicative cycle
Nisole, S., & Saı̈b, A. (2004) · Retrovirology · doi:10.1186/1742-4690-1-9 · Cited by 202 · see citing works
“Finally, the cellular protein cyclophilin A (CypA), which is incorporated into virions through its interaction with viral capsid [111-113], has been shown to play a critical role in the correct disassembly of the HIV-1 cores early after infection [114], since particles lacking CypA display a defect between entry and r…”
Background
A putative α-helical structure which overlaps the capsid-p2 boundary in the human immunodeficiency virus type 1 Gag precursor is crucial for viral particle assembly
Accola, M. A., Höglund, S., & Göttlinger, H. G. (1998) · Journal of Virology · doi:10.1128/jvi.72.3.2072-2078.1998 · Cited by 196 · see citing works
“An exposed loop region between two a-helices interacts with the prolyl isomerase cyclophilin A (14), which leads to the incorporation of the cellular enzyme into virions (13, 48).”
Background
Cyclophilin Interactions with Incoming Human Immunodeficiency Virus Type 1 Capsids with Opposing Effects on Infectivity in Human Cells
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“Crystal structure analysis reveals that a proline-rich stretch of the single exposed loop of HIV-1 CA interacts with the catalytic domain of the isomerase (Gamble et al., 1996).”
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Amino Acid Substitutions in Gag Protein at Non-cleavage Sites Are Indispensable for the Development of a High Multitude of HIV-1 Resistance against Protease Inhibitors
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“Binding of CypA to the viral capsid is normally necessary for efficient infection by HIV-1 and is believed to regulate the uncoating process or to impair recognition of the capsid by host restriction factors (10, 19, 21, 58).”
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Conformation of the HIV-1 Gag Protein in Solution
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Human Immunodeficiency Virus Type 1 N-Terminal Capsid Mutants That Exhibit Aberrant Core Morphology and Are Blocked in Initiation of Reverse Transcription in Infected Cells
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Human and Simian Immunodeficiency Virus Capsid Proteins Are Major Viral Determinants of Early, Postentry Replication Blocks in Simian Cells
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Structure of the Amino-Terminal Core Domain of the HIV-1 Capsid Protein
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Self-citation
Crystal structure of cyclophilin A complexed with a binding site peptide from the HIV‐1 capsid protein
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The Cysteine Residues of HIV-1 Capsid Regulate Oligomerization and Cyclophilin A-Induced Changes
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Cyclophilin a Stabilizes the Mature HIV-1 Capsid through a Novel Non-Canonical Binding Site
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Catalysis and Binding of Cyclophilin A with Different HIV-1 Capsid Constructs
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Authors: Gamble, T. R., Vajdos, F. F., Yoo, S., Worthylake, D. K., Houseweart, M., Sundquist, W. I., & Hill, C. P.
Affiliations: University of Utah (US)
Corresponding author: Hill, Christopher P
ORCID: Gamble, Theresa R
Vajdos, Felix F
Yoo, Sanghee
Sundquist, Wesley I
Hill, Christopher P
Venue: Cell
Publisher: Elsevier BV
Published: 1996-12
Volume: 87
Issue: 7
Pages: 1285-1294
ISSN: 0092-8674 (ISSN-L)
DOI: 10.1016/s0092-8674(00)81823-1
OpenAlex: W2121753315
Cited by: 706
References: 59
Citations by year: 2026: 12 · 2025: 8 · 2024: 7 · 2023: 18 · 2022: 20 · 2021: 26 · 2020: 16 · 2019: 12 · 2018: 23 · 2017: 21 · 2016: 29 · 2015: 22 · 2014: 25 · 2013: 32 · 2012: 24
FWCI: 6.27
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 6072 d)
Locations: Cell (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Signaling Pathways in Disease
Health Sciences › Medicine › Infectious Diseases › HIV/AIDS drug development and treatment
Keywords: cyclophilin A, HIV-1 capsid, peptidyl-prolyl isomerase, protein-protein complex, capsid disassembly, viral core, capsid assembly, HIV-1 replication
MeSH terms: Amino Acid Isomerases, Capsid, Carrier Proteins, Humans, Models, Molecular, Protein Binding, Virion, HIV-1, Gene Products, gag, Protein Structure, Tertiary, Crystallography, X-Ray, Peptidylprolyl Isomerase

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Crystal Structure of Human Cyclophilin A Bound to the Amino-Terminal Domain of HIV-1 Capsid

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