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| | ==C1s CUB1-EGF-CUB2 in complex with a collagen-like peptide from C1q== | | ==C1s CUB1-EGF-CUB2 in complex with a collagen-like peptide from C1q== |
| - | <StructureSection load='4lor' size='340' side='right' caption='[[4lor]], [[Resolution|resolution]] 2.50Å' scene=''> | + | <StructureSection load='4lor' size='340' side='right'caption='[[4lor]], [[Resolution|resolution]] 2.50Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4lor]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4LOR OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4LOR FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4lor]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4LOR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4LOR FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=HYP:4-HYDROXYPROLINE'>HYP</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene></td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=HYP:4-HYDROXYPROLINE'>HYP</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene></td></tr>
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4lor FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4lor OCA], [https://pdbe.org/4lor PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4lor RCSB], [https://www.ebi.ac.uk/pdbsum/4lor PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4lor ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">C1S ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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_C1s Complement subcomponent C1s], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.42 3.4.21.42] </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=4lor FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4lor OCA], [http://pdbe.org/4lor PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4lor RCSB], [http://www.ebi.ac.uk/pdbsum/4lor PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4lor ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Disease == | | == 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. | + | [https://www.uniprot.org/uniprot/C1S_HUMAN C1S_HUMAN] Defects in C1S are the cause of complement component C1s deficiency (C1SD) [MIM:[https://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 == | | == Function == |
| - | [[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. | + | [https://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;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Complement subcomponent C1s]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Human]] | + | [[Category: Large Structures]] |
| - | [[Category: Girija, U Venkatraman]] | + | [[Category: Marshall JE]] |
| - | [[Category: Marshall, J E]] | + | [[Category: Moody PCE]] |
| - | [[Category: Moody, P C.E]] | + | [[Category: Venkatraman Girija U]] |
| - | [[Category: Wallis, R]] | + | [[Category: Wallis R]] |
| - | [[Category: C1 complex]]
| + | |
| - | [[Category: Cub domain]]
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| - | [[Category: Egf-like domain]]
| + | |
| - | [[Category: Hydrolase-protein binding complex]]
| + | |
| - | [[Category: Protein collagen complex]]
| + | |
| Structural highlights
4lor is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | , , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Disease
C1S_HUMAN Defects in C1S are the cause of complement component C1s deficiency (C1SD) [MIM: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
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.
Publication Abstract from PubMed
Complement component C1, the complex that initiates the classical pathway of complement activation, is a 790-kDa assembly formed from the target-recognition subcomponent C1q and the modular proteases C1r and C1s. The proteases are elongated tetramers that become more compact when they bind to the collagen-like domains of C1q. Here, we describe a series of structures that reveal how the subcomponents associate to form C1. A complex between C1s and a collagen-like peptide containing the C1r/C1s-binding motif of C1q shows that the collagen binds to a shallow groove via a critical lysine side chain that contacts Ca(2+)-coordinating residues. The data explain the Ca(2+)-dependent binding mechanism, which is conserved in C1r and also in mannan-binding lectin-associated serine proteases, the serine proteases of the lectin pathway activation complexes. In an accompanying structure, C1s forms a compact ring-shaped tetramer featuring a unique head-to-tail interaction at its center that replicates the likely arrangement of C1r/C1s polypeptides in the C1 complex. Additional structures reveal how C1s polypeptides are positioned to enable activation by C1r and interaction with the substrate C4 inside the cage-like assembly formed by the collagenous stems of C1q. Together with previously determined structures of C1r fragments, the results reported here provide a structural basis for understanding the early steps of complement activation via the classical pathway.
Structural basis of the C1q/C1s interaction and its central role in assembly of the C1 complex of complement activation.,Venkatraman Girija U, Gingras AR, Marshall JE, Panchal R, Sheikh MA, Gal P, Schwaeble WJ, Mitchell DA, Moody PC, Wallis R Proc Natl Acad Sci U S A. 2013 Aug 20;110(34):13916-20. doi:, 10.1073/pnas.1311113110. Epub 2013 Aug 6. PMID:23922389[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Venkatraman Girija U, Gingras AR, Marshall JE, Panchal R, Sheikh MA, Gal P, Schwaeble WJ, Mitchell DA, Moody PC, Wallis R. Structural basis of the C1q/C1s interaction and its central role in assembly of the C1 complex of complement activation. Proc Natl Acad Sci U S A. 2013 Aug 20;110(34):13916-20. doi:, 10.1073/pnas.1311113110. Epub 2013 Aug 6. PMID:23922389 doi:10.1073/pnas.1311113110
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