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PDBsum entry 4los
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References listed in PDB file
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Key reference
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Title
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Structural basis of the c1q/c1s interaction and its central role in assembly of the c1 complex of complement activation.
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Authors
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U.Venkatraman girija,
A.R.Gingras,
J.E.Marshall,
R.Panchal,
M.A.Sheikh,
P.Gál,
W.J.Schwaeble,
D.A.Mitchell,
P.C.Moody,
R.Wallis.
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Ref.
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Proc Natl Acad Sci U S A, 2013,
110,
13916-13920.
[DOI no: ]
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PubMed id
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Abstract
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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.
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