Helical Assembly in the MyD88-IRAK4-IRAK2 Complex in TLR/IL-1R Signalling
Open accessAbstract
MyD88, IRAK4 and IRAK2 are critical signalling mediators of the TLR/IL1-R superfamily. Here we report the crystal structure of the MyD88-IRAK4-IRAK2 death domain (DD) complex, which surprisingly reveals a left-handed helical oligomer that consists of 6 MyD88, 4 IRAK4 and 4 IRAK2 DDs. Assembly of this helical signalling tower is hierarchical, in which MyD88 recruits IRAK4 and the MyD88-IRAK4 complex recruits the IRAK4 substrates IRAK2 or the related IRAK1. Formation of these Myddosome complexes brings the kinase domains of IRAKs into proximity for phosphorylation and activation. Composite binding sites are required for recruitment of the individual DDs in the complex, which are confirmed by mutagenesis and previously identified signalling mutations. Specificities in Myddosome formation are dictated by both molecular complementarity and correspondence of surface electrostatics. The MyD88-IRAK4-IRAK2 complex provides a template for Toll signalling in Drosophila and an elegant mechanism for versatile assembly and regulation of DD complexes in signal transduction.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
TLR9 activation induces assembly of the myddosome involving MyD88 and multiple members of the serine threonine kinase family IRAK.
“TLR9 activation induces the assembly of a supramolecular organizing center called the myddosome, involving MyD88 and multiple members of the serine threonine kinase family IRAK [82,83].”
From Risk mitigation of immunogenicity: a key to personalized retinal gene therapy (2021) · cites this paper as [82]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
[20] Processing of X-ray diffraction data collected in oscillation mode
Otwinowski, Z., & Minor, W. (1997) · Methods in Enzymology · doi:10.1016/s0076-6879(97)76066-x · Cited by 33,475 · see citing works
<i>Coot</i> : model-building tools for molecular graphics
Emsley, P., & Cowtan, K. (2004) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444904019158 · Cited by 30,571 · see citing works
The PyMOL Molecular Graphics System
DeLano, W. L. (2002) · Medical Entomology and Zoology · Cited by 18,147 · see citing works
The CCP4 suite: programs for protein crystallography
Number Collaborative Computational Project (1994) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444994003112 · Cited by 17,299 · see citing works
Crystallography & NMR System: A New Software Suite for Macromolecular Structure Determination
Brünger, A. T., Adams, P. D., Clore, G. M., DeLano, W. L., Gros, P., Grosse‐Kunstleve, R. W., Jiang, J., Kuszewski, J. J., Nilges, M., Pannu, N., et al. (1998) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444998003254 · Cited by 15,720 · see citing works
Pathogen Recognition and Innate Immunity
Akira, S., Uematsu, S., & Takeuchi, O. (2006) · Cell · doi:10.1016/j.cell.2006.02.015 · Cited by 11,974 · see citing works
Takeda, K., Kaisho, T., & Akira, S. (2003) · Annual Review of Immunology · doi:10.1146/annurev.immunol.21.120601.141126 · Cited by 6,143 · see citing works
<i>PHENIX</i> : building new software for automated crystallographic structure determination
Adams, P. D., Grosse-Kunstleve, R. W., Hung, L.-W., Ioerger, T. R., McCoy, A. J., Moriarty, N. W., Read, R. J., Sacchettini, J. C., Sauter, N. K., & Terwilliger, T. C. (2002) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444902016657 · Cited by 4,361 · see citing works
The family of five: TIR-domain-containing adaptors in Toll-like receptor signalling
O'Neill, L. A. J., & Bowie, A. G. (2007) · Nature Reviews Immunology · doi:10.1038/nri2079 · Cited by 2,667 · see citing works
Unresponsiveness of MyD88-deficient mice to endotoxin.
Kawai, T., Adachi, O., Ogawa, T., Takeda, K., & Akira, S. (1999) · Immunity · doi:10.1016/s1074-7613(00)80086-2 · Cited by 2,367 · see citing works
Plasmacytoid dendritic cells sense self-DNA coupled with antimicrobial peptide
Lande, R., Gregorio, J., Facchinetti, V., Chatterjee, B., Wang, Y.-H., Homey, B., Cao, W., Wang, Y.-H., Su, B., Nestle, F. O., et al. (2007) · Nature · doi:10.1038/nature06116 · Cited by 1,910 · see citing works
Stewart, C. R., Stuart, L. M., Wilkinson, K., van Gils, J. M., Deng, J., Halle, A., Rayner, K. J., Boyer, L., Zhong, R., Frazier, W. A., et al. (2010) · Nature Immunology · doi:10.1038/ni.1836 · Cited by 1,513 · see citing works
Dali: a network tool for protein structure comparison
Holm, L., & Sander, C. (1995) · Trends in Biochemical Sciences · doi:10.1016/s0968-0004(00)89105-7 · Cited by 1,462 · see citing works
Inferences, questions and possibilities in Toll-like receptor signalling
Beutler, B. (2004) · Nature · doi:10.1038/nature02761 · Cited by 1,458 · see citing works
TRAF6 is a signal transducer for interleukin-1
Cao, Z., Xiong, J., Takeuchi, M., Kurama, T., & Goeddel, D. V. (1996) · Nature · doi:10.1038/383443a0 · Cited by 1,305 · see citing works
IRAK-M Is a Negative Regulator of Toll-like Receptor Signaling
Kobayashi, K. S., Hernandez, L. D., Galán, J. E., Janeway, C. A., Medzhitov, R. M., & Flavell, R. A. (2002) · Cell · doi:10.1016/s0092-8674(02)00827-9 · Cited by 1,289 · see citing works
Pyogenic Bacterial Infections in Humans with MyD88 Deficiency
von Bernuth, H., Pïcard, C., Jin, Z., Sranujit, R. P., Xiao, H. Q., Ku, C., Chrabieh, M., Ben‐Mustapha, I., Ghandil, P., Çamcıoğlu, Y., et al. (2008) · Science · doi:10.1126/science.1158298 · Cited by 1,287 · see citing works
Shape Complementarity at Protein/Protein Interfaces
Lawrence, M. C., & Colman, P. M. (1993) · Journal of Molecular Biology · doi:10.1006/jmbi.1993.1648 · Cited by 1,219 · see citing works
Shape complementarity at protein–protein interfaces
Norel, R., Lin, S. L., Wolfson, H. J., & Nussinov, R. (1994) · Biopolymers · doi:10.1002/bip.360340711 · Cited by 1,208 · see citing works
Self-citationAutoreactive B Cell Responses to RNA-Related Antigens Due to TLR7 Gene Duplication
Pisitkun, P., Deane, J., Difilippantonio, M., Tarasenko, T. N., Satterthwaite, A., & Bolland, S. (2006) · Science · doi:10.1126/science.1124978 · Cited by 950 · see citing works
Severe impairment of interleukin-1 and Toll-like receptor signalling in mice lacking IRAK-4
Suzuki, N., Suzuki, S., Duncan, G. S., Millar, D. G., Wada, T., Mirtsos, C., Takada, H., Wakeham, A. C., Itié, A., Li, S., et al. (2002) · Nature · doi:10.1038/nature736 · Cited by 858 · see citing works
A CONSERVED SIGNALING PATHWAY: The <i>Drosophila</i> Toll-Dorsal Pathway
Belvin, M. P., & Anderson, K. V. (1996) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev.cellbio.12.1.393 · Cited by 836 · see citing works
Pyogenic Bacterial Infections in Humans with IRAK-4 Deficiency
Pïcard, C., Puel, A., Bonnet, M., Ku, C., Bustamante, J. C., Yang, K., Soudais, C., Boisson‐Dupuis, S., Feinberg, J. M., Fieschi, C., et al. (2003) · Science · doi:10.1126/science.1081902 · Cited by 828 · see citing works
GENETIC ANALYSIS OF HOST RESISTANCE: Toll-Like Receptor Signaling and Immunity at Large
Beutler, B., Jiang, Z., Georgel, P., Crozat, K., Croker, B. A., Rutschmann, S., Du, X., & Hoebe, K. H. N. (2006) · Annual Review of Immunology · doi:10.1146/annurev.immunol.24.021605.090552 · Cited by 772 · see citing works
Interleukin-1, Interleukin-1 Receptors and Interleukin-1 Receptor Antagonist
Dinarello, C. A. (1998) · International Reviews of Immunology · doi:10.3109/08830189809043005 · Cited by 761 · see citing works
IRAK-4: A novel member of the IRAK family with the properties of an IRAK-kinase
Li, S., Strelow, A., Fontana, E. J., & Wesche, H. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.082100399 · Cited by 714 · see citing works
Dunne, A., & O'Neill, L. A. J. (2003) · Science s STKE · doi:10.1126/stke.2003.171.re3 · Cited by 712 · see citing works
The interleukin‐1 receptor/Toll‐like receptor superfamily: 10 years of progress
O'Neill, L. A. J. (2008) · Immunological Reviews · doi:10.1111/j.1600-065x.2008.00701.x · Cited by 612 · see citing works
Dasu, M. R., Devaraj, S., Park, S., & Jialal, I. (2010) · Diabetes Care · doi:10.2337/dc09-1799 · Cited by 572 · see citing works
The Death Domain Superfamily in Intracellular Signaling of Apoptosis and Inflammation
Park, H. H., Lo, Y.-C., Lin, S., Wang, L., Yang, J. K., & Wu, H. (2007) · Annual Review of Immunology · doi:10.1146/annurev.immunol.25.022106.141656 · Cited by 523 · see citing works
Self-citationBurns, K., Janssens, S., Brissoni, B., Olivos, N., Beyaert, R., & Tschopp, J. (2003) · The Journal of Experimental Medicine · doi:10.1084/jem.20021790 · Cited by 512 · see citing works
Bowie, A., & O'Neill, L. A. J. (2000) · Journal of Leukocyte Biology · doi:10.1002/jlb.67.4.508 · Cited by 495 · see citing works
Sequential control of Toll-like receptor–dependent responses by IRAK1 and IRAK2
Kawagoe, T., Sato, S., Matsushita, K., Kato, H., Matsui, K., Kumagai, Y., Saitoh, T., Kawai, T., Takeuchi, O., & Akira, S. (2008) · Nature Immunology · doi:10.1038/ni.1606 · Cited by 443 · see citing works
SOLVE and RESOLVE: automated structure solution, density modification and model building
Terwilliger, T. C. (2003) · Journal of Synchrotron Radiation · doi:10.1107/s0909049503023938 · Cited by 406 · see citing works
Motshwene, P. G., Moncrieffe, M. C., Grossmann, J. G., Kao, C. C., Murali, A., Sandercock, A. M., Robinson, C. V., Latz, E., & Gay, N. J. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.022392 · Cited by 394 · see citing works
Automated structure solution, density modification and model building
Terwilliger, T. C. (2002) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444902016438 · Cited by 285 · see citing works
Park, H. H., Logette, E., Raunser, S., Cuenin, S., Walz, T., Tschopp, J., & Wu, H. (2007) · Cell · doi:10.1016/j.cell.2007.01.019 · Cited by 280 · see citing works
Self-citationConze, D. B., Wu, C.-J., Thomas, J. A., Landstrom, A., & Ashwell, J. D. (2008) · Molecular and Cellular Biology · doi:10.1128/mcb.02098-07 · Cited by 237 · see citing works
Cancers take their Toll—the function and regulation of Toll-like receptors in cancer cells
Chen, R. J., Alvero, A. B., Silasi, D.-A., Steffensen, K. D., & Mor, G. (2008) · Oncogene · doi:10.1038/sj.onc.1210907 · Cited by 200 · see citing works
Janssens, S., Burns, K., Vercammen, E., Tschopp, J., & Beyaert, R. (2003) · FEBS Letters · doi:10.1016/s0014-5793(03)00747-6 · Cited by 195 · see citing works
ProtorP: a protein–protein interaction analysis server
Reynolds, C. R., Damerell, D., & Jones, S. (2008) · Bioinformatics · doi:10.1093/bioinformatics/btn584 · Cited by 185 · see citing works
Toll like receptor 4 in atherosclerosis and plaque destabilization
den Dekker, W. K., Cheng, C., Pasterkamp, G., & Duckers, H. J. (2009) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2009.09.075 · Cited by 171 · see citing works
Three-Dimensional Structure of a Complex between the Death Domains of Pelle and Tube
Xiao, T. S., Towb, P., Wasserman, S. A., & Sprang, S. R. (1999) · Cell · doi:10.1016/s0092-8674(00)81542-1 · Cited by 171 · see citing works
A heterotrimeric death domain complex in Toll signaling
Sun, H.-Y., Bristow, B. N., Qu, G.-W., & Wasserman, S. (2002) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.202396399 · Cited by 165 · see citing works
Neuroimmune interactions and pain: focus on glial-modulating targets.
Romero-Sandoval, E. A., Horvath, R. J., & DeLeo, J. A. (2008) · PubMed · Cited by 140 · see citing works
Szabó, G., Dolganiuc, A., Dai, Q., & Pruett, S. B. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.178.3.1243 · Cited by 137 · see citing works
Regulated assembly of the Toll signaling complex drives Drosophila dorsoventral patterning
Sun, H.-Y., Towb, P., Chiem, D. N., Foster, B. A., & Wasserman, S. A. (2004) · EMBO Journal · doi:10.1038/sj.emboj.7600033 · Cited by 112 · see citing works
The Murine Irak2 Gene Encodes Four Alternatively Spliced Isoforms, Two of Which Are Inhibitory
Hardy, M. P., & O'Neill, L. A. J. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m403068200 · Cited by 107 · see citing works
Rao, N. L., Nguyen, S. M., Ngo, K., & Fung‐Leung, W. (2005) · Molecular and Cellular Biology · doi:10.1128/mcb.25.15.6521-6532.2005 · Cited by 103 · see citing works
Primer: Toll-like receptor signaling pathways—what do rheumatologists need to know?
O'Neill, L. A. J. (2008) · Nature Clinical Practice Rheumatology · doi:10.1038/ncprheum0802 · Cited by 92 · see citing works
Wan, Y., Xiao, H. Q., Affolter, J. T., Kim, T. W., Bulek, K., Chaudhuri, S., Carlson, D., Hamilton, T. A., Mazumder, B., Stark, G. R., et al. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m807822200 · Cited by 89 · see citing works
Loiarro, M., Gallo, G., Fantò, N., Santis, R. D., Carminati, P., Ruggiero, V., & Sette, C. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.004465 · Cited by 82 · see citing works
Regulation of autoimmune encephalomyelitis by toll-like receptors.
Marta, M., Meier, U., & Lobell, A. (2009) · Autoimmunity Reviews · doi:10.1016/j.autrev.2009.01.006 · Cited by 81 · see citing works
Assembly of Oligomeric Death Domain Complexes during Toll Receptor Signaling*
Moncrieffe, M. C., Grossmann, J. G., & Gay, N. J. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m805427200 · Cited by 74 · see citing works
Toll-like receptor signalling and the clinical benefits that lie within
Verstak, B., Hertzog, P. J., & Mansell, A. S. (2007) · Inflammation Research · doi:10.1007/s00011-007-6093-7 · Cited by 69 · see citing works
Tube Is an IRAK-4 Homolog in a Toll Pathway Adapted for Development and Immunity
Towb, P., Sun, H.-Y., & Wasserman, S. (2009) · Journal of Innate Immunity · doi:10.1159/000200773 · Cited by 57 · see citing works
Lasker, M. V., Gajjar, M. M., & Nair, S. K. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.175.7.4175 · Cited by 47 · see citing works
Single-particle reconstruction from EM images of helical filaments
Egelman, E. H. (2007) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2007.07.006 · Cited by 38 · see citing works
Horner, A. A., & Raz, E. (2003) · Current Opinion in Immunology · doi:10.1016/j.coi.2003.09.021 · Cited by 37 · see citing works
Puzzling Out the Pains in the Gut
Marx, J. L. (2007) · Science · doi:10.1126/science.315.5808.33 · Cited by 20 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Toll-like Receptors and the Control of Immunity
Fitzgerald, K. A., & Kagan, J. C. (2020) · Cell · doi:10.1016/j.cell.2020.02.041 · Cited by 2,168 · see citing works
Li, J., McQuade, T., Siemer, A. B., Napetschnig, J., Moriwaki, K., Hsiao, Y.-S., Damko, E., Moquin, D., Walz, T., McDermott, A., et al. (2012) · Cell · doi:10.1016/j.cell.2012.06.019 · Cited by 1,222 · see citing works
Self-citationAssembly and localization of Toll-like receptor signalling complexes
Gay, N. J., Symmons, M. F., Gangloff, M., & Bryant, C. E. (2014) · Nature Reviews Immunology · doi:10.1038/nri3713 · Cited by 832 · see citing works
MyD88: a central player in innate immune signaling
Deguine, J., & Barton, G. M. (2014) · F1000Prime Reports · doi:10.12703/p6-97 · Cited by 692 · see citing works
The IκB kinase complex in NF‐κB regulation and beyond
Hinz, M., & Scheidereit, C. (2014) · The EMBO Reports · doi:10.1002/embr.201337983 · Cited by 572 · see citing works
Moresco, E. M. Y., LaVine, D., & Beutler, B. (2011) · Current Biology · doi:10.1016/j.cub.2011.05.039 · Cited by 500 · see citing works
Kinase inhibition in autoimmunity and inflammation
Zarrin, A. A., Bao, K., Lupardus, P., & Vucic, D. (2021) · Nature Reviews Drug Discovery · doi:10.1038/s41573-020-0082-8 · Cited by 431 · see citing works
The emerging role of Toll-like receptor 4 in myocardial inflammation
Yang, Y., Lv, J., Jiang, S., Ma, Z., Wang, D., Hu, W., Deng, C., Fan, C., Di, S., Sun, Y., et al. (2016) · Cell Death & Disease · doi:10.1038/cddis.2016.140 · Cited by 337 · see citing works
Toll-like receptors in the pathogenesis of neuroinflammation
Kumar, V. (2019) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2019.03.012 · Cited by 331 · see citing works
PROTACs: great opportunities for academia and industry (an update from 2020 to 2021)
He, M., Cao, C., Ni, Z., Liu, Y., Song, P., Hao, S., He, Y., Sun, X., & Rao, Y. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-00999-9 · Cited by 283 · see citing works
Microglia in Parkinson's disease
Ho, M. S. (2019) · Advances in Experimental Medicine and Biology · doi:10.1007/978-981-13-9913-8_13 · Cited by 227 · see citing works
Fu, T.-M., Li, Y., Lu, A., Li, Z., Vajjhala, P. R., Cruz, A. C., Srivastava, D. B., DiMaio, F., Penczek, P. A., Siegel, R. M., et al. (2016) · Molecular Cell · doi:10.1016/j.molcel.2016.09.009 · Cited by 196 · see citing works
Self-citationStructural studies of NF-κB signaling
Zheng, C., Yin, Q., & Wu, H. (2011) · Cell Research · doi:10.1038/cr.2010.171 · Cited by 134 · see citing works
Self-citationHung, Y.-F., Chen, C.-Y., Shih, Y.-C., Liu, H.-Y., Huang, C.-M., & Hsueh, Y.-P. (2018) · Journal of Cell Biology · doi:10.1083/jcb.201712113 · Cited by 86 · see citing works
Two Human MYD88 Variants, S34Y and R98C, Interfere with MyD88-IRAK4-Myddosome Assembly
George, J., Motshwene, P. G., Wang, H., Kubarenko, A. V., Rautanen, A., Mills, T. C., Hill, A. V. S., Gay, N. J., & Weber, A. N. R. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.159996 · Cited by 66 · see citing works
Assessing IRAK4 Functions in ABC DLBCL by IRAK4 Kinase Inhibition and Protein Degradation
Zhang, J., Fu, L., Shen, B., Liu, Y., Wang, W., Cai, X., Kong, L., Yan, Y., Meng, R., Zhang, Z., et al. (2020) · Cell Chemical Biology · doi:10.1016/j.chembiol.2020.08.010 · Cited by 63 · see citing works
Investigational IRAK-4 inhibitors for the treatment of rheumatoid arthritis
Wiese, M. D., Manning-Bennett, A. T., & Abuhelwa, A. Y. (2020) · Expert Opinion on Investigational Drugs · doi:10.1080/13543784.2020.1752660 · Cited by 58 · see citing works
Trends in adjuvant development for vaccines: DAMPs and PAMPs as potential new adjuvants
Miyaji, E. N., Carvalho, E., Oliveira, M. L. S., Raw, I., & Ho, P. L. (2011) · Brazilian Journal of Medical and Biological Research · doi:10.1590/s0100-879x2011007500064 · Cited by 66 · see citing works
“The first one involves the adaptor molecules TIRAP and MyD88 when pathogen-induced dimerization of TLR4 recruits MyD88 molecules and IRAK kinase enzymes that hierarchically assemble into a left-handed helical oligomerized tower for proper signal transduction, triggering NF-κB activation and pro-inflammatory cytokine g…”
BackgroundStructural Basis for Recruitment of DAPK1 to the KLHL20 E3 Ligase
Chen, Z., Picaud, S., Filippakopoulos, P., D'Angiolella, V., & Bullock, A. N. (2019) · Structure · doi:10.1016/j.str.2019.06.005 · Cited by 37 · see citing works
Modifying immune responses to adeno-associated virus vectors by capsid engineering
Bentler, M., Hardet, R., Ertelt, M., Rudolf, D., Kaniowska, D., Schneider, A., Vondran, F. W. R., Schoeder, C. T., Delphin, M., Lucifora, J., et al. (2023) · Molecular Therapy - Methods & Clinical Development · doi:10.1016/j.omtm.2023.08.015 · Cited by 34 · see citing works
Risk mitigation of immunogenicity: a key to personalized retinal gene therapy
Varin, J., Morival, C., Maillard, N., Adjali, O., & Cronin, T. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms222312818 · Cited by 19 · see citing works
- Authors
- Lin, S.-C., Lo, Y.-C., & Wu, H.
- Affiliations
- Weill Cornell Medicine (US)
- Corresponding author
- Wu, Hao
- Venue
- Nature
- Published
- 2010-05-19
- Volume
- 465
- Issue
- 7300
- Pages
- 885-890
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC2888693
- OpenAlex
- W1993211211
- Cited by
- 1,111
- References
- 60
- Citations by year
- 2026: 48 · 2025: 64 · 2024: 61 · 2023: 61 · 2022: 69 · 2021: 73 · 2020: 91 · 2019: 82 · 2018: 75 · 2017: 75 · 2016: 77 · 2015: 55 · 2014: 87 · 2013: 67 · 2012: 58
- FWCI
- 26.26
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- National Institute of Allergy and Infectious Diseases (R01AI050872)
- National Institute of Biomedical Imaging and Bioengineering (P30EB009998)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
- Keywords
- MyD88, IRAK4, IRAK2, death domain, Toll-like receptors, Myddosome, ternary protein complex, innate immunity, kinase activation, surface electrostatics
- MeSH terms
- Humans, Models, Molecular, Signal Transduction, Protein Structure, Tertiary, Receptors, Interleukin-1, Toll-Like Receptors, Interleukin-1 Receptor-Associated Kinases, Myeloid Differentiation Factor 88
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
