4lor

C1s CUB1-EGF-CUB2 in complex with a collagen-like peptide from C1q

spinqualitylabelsall models 4lor, resolution 2.50Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D 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. Method: X-ray diffraction, Resolution 2.5Å Ligands: ACE, CA, HYP, NA, NAG, NH2 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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