6f1c: Difference between revisions
New page: '''Unreleased structure''' The entry 6f1c is ON HOLD Authors: Almitairi, J.O.M., Venkatraman Girija, U., Furze, C.M., Simpson-Gray, X., Badakshi, F., Marshall, J.E., Mitchell, D.A., Moo... |
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The | ==C1rC1s complex== | ||
<StructureSection load='6f1c' size='340' side='right' caption='[[6f1c]], [[Resolution|resolution]] 4.20Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6f1c]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6F1C OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6F1C FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=GAL:BETA-D-GALACTOSE'>GAL</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr> | |||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Complement_subcomponent_C1r Complement subcomponent C1r], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.41 3.4.21.41] </span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6f1c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6f1c OCA], [http://pdbe.org/6f1c PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6f1c RCSB], [http://www.ebi.ac.uk/pdbsum/6f1c PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6f1c ProSAT]</span></td></tr> | |||
</table> | |||
== Disease == | |||
[[http://www.uniprot.org/uniprot/C1S_HUMAN C1S_HUMAN]] Defects in C1S are the cause of complement component C1s deficiency (C1SD) [MIM:[http://omim.org/entry/613783 613783]]. A rare defect resulting in C1 deficiency and impaired activation of the complement classical pathway. C1 deficiency generally leads to severe immune complex disease with features of systemic lupus erythematosus and glomerulonephritis. | |||
== Function == | |||
[[http://www.uniprot.org/uniprot/C1R_HUMAN C1R_HUMAN]] C1r B chain is a serine protease that combines with C1q and C1s to form C1, the first component of the classical pathway of the complement system. [[http://www.uniprot.org/uniprot/C1S_HUMAN C1S_HUMAN]] C1s B chain is a serine protease that combines with C1q and C1r to form C1, the first component of the classical pathway of the complement system. C1r activates C1s so that it can, in turn, activate C2 and C4. | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The multiprotein complex C1 initiates the classical pathway of complement activation on binding to antibody-antigen complexes, pathogen surfaces, apoptotic cells, and polyanionic structures. It is formed from the recognition subcomponent C1q and a tetramer of proteases C1r2C1s2 as a Ca(2+)-dependent complex. Here we have determined the structure of a complex between the CUB1-EGF-CUB2 fragments of C1r and C1s to reveal the C1r-C1s interaction that forms the core of C1. Both fragments are L-shaped and interlock to form a compact antiparallel heterodimer with a Ca(2+) from each subcomponent at the interface. Contacts, involving all three domains of each protease, are more extensive than those of C1r or C1s homodimers, explaining why heterocomplexes form preferentially. The available structural and biophysical data support a model of C1r2C1s2 in which two C1r-C1s dimers are linked via the catalytic domains of C1r. They are incompatible with a recent model in which the N-terminal domains of C1r and C1s form a fixed tetramer. On binding to C1q, the proteases become more compact, with the C1r-C1s dimers at the center and the six collagenous stems of C1q arranged around the perimeter. Activation is likely driven by separation of the C1r-C1s dimer pairs when C1q binds to a surface. Considerable flexibility in C1s likely facilitates C1 complex formation, activation of C1s by C1r, and binding and activation of downstream substrates C4 and C4b-bound C2 to initiate the reaction cascade. | |||
Structure of the C1r-C1s interaction of the C1 complex of complement activation.,Almitairi JOM, Venkatraman Girija U, Furze CM, Simpson-Gray X, Badakshi F, Marshall JE, Schwaeble WJ, Mitchell DA, Moody PCE, Wallis R Proc Natl Acad Sci U S A. 2018 Jan 8. pii: 1718709115. doi:, 10.1073/pnas.1718709115. PMID:29311313<ref>PMID:29311313</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 6f1c" style="background-color:#fffaf0;"></div> | ||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Complement subcomponent C1r]] | |||
[[Category: Almitairi, J O.M]] | |||
[[Category: Badakshi, F]] | [[Category: Badakshi, F]] | ||
[[Category: Furze, C M]] | |||
[[Category: Girija, U Venkatraman]] | |||
[[Category: Marshall, J E]] | |||
[[Category: Mitchell, D A]] | |||
[[Category: Moody, P C.E]] | |||
[[Category: Simpson-Gray, X]] | [[Category: Simpson-Gray, X]] | ||
[[Category: Wallis, R]] | [[Category: Wallis, R]] | ||
[[Category: | [[Category: C1r-c1]] | ||
[[Category: Complement]] | |||
[[Category: Cub domain]] | |||
[[Category: Egf-like domain]] | |||
[[Category: Hydrolase]] | |||