4LMF

C1s CUB1-EGF-CUB2

Summary for 4LMF

• Entry DOI: 10.2210/pdb4lmf/pdb
• Related: 4LOR 4LOS 4LOT
• Descriptor: Complement C1s subcomponent heavy chain, SODIUM ION, CALCIUM ION (3 entities in total)
• Functional Keywords: cub domain, egf-like domain, complement c1s, hydrolase
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 4
• Total formula weight: 125034.86

Authors

Wallis, R.,Venkatraman Girija, U.,Moody, P.C.E.,Marshall, J.E. (deposition date: 2013-07-10, release date: 2013-08-07, Last modification date: 2024-10-30)

Primary citation

Venkatraman Girija, U.,Gingras, A.R.,Marshall, J.E.,Panchal, R.,Sheikh, M.A.,Gal, P.,Schwaeble, W.J.,Mitchell, D.A.,Moody, P.C.,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.USA, 110:13916-13920, 2013

PubMed Abstract: 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.

PubMed: 23922389
DOI: 10.1073/pnas.1311113110

Experimental method

X-RAY DIFFRACTION (2.921 Å)