4b0f
Heptameric core complex structure of C4b-binding (C4BP) protein from human
Structural highlights
FunctionC4BPA_HUMAN Controls the classical pathway of complement activation. It binds as a cofactor to C3b/C4b inactivator (C3bINA), which then hydrolyzes the complement fragment C4b. It also accelerates the degradation of the C4bC2a complex (C3 convertase) by dissociating the complement fragment C2a. Alpha chain binds C4b. It interacts also with anticoagulant protein S and with serum amyloid P component. Publication Abstract from PubMedThe complement system as major part of innate immunity is the first line of defense against invading microorganisms. Orchestrated by more than 60 proteins, its major task is to discriminate between host cells and pathogens and to initiate immune response. Additional recognition of necrotic or apoptotic cells demand a fine-tune regulation of this powerful system. C4b-binding protein (C4BP) is the major inhibitor of the classical complement and lectin pathway. The crystal structure of the human C4BP oligomerization domain in its 7alpha isoform and molecular simulations provide first structural insights of C4BP oligomerization. The heptameric core structure is stabilized by intermolecular disulfide bonds. In addition, thermal shift assays indicate that layers of electrostatic interactions mainly contribute to the extraordinary thermodynamic stability of the complex. These findings make C4BP a promising scaffold for multivalent ligand display with applications in immunology and biological chemistry. Arranged sevenfold: structural insights into the C-terminal oligomerization domain of human C4b-binding protein.,Hofmeyer T, Schmelz S, Degiacomi MT, Peraro MD, Daneschdar M, Scrima A, den Heuvel JV, Heinz DW, Kolmar H J Mol Biol. 2012 Dec 27. pii: S0022-2836(12)00950-3. doi:, 10.1016/j.jmb.2012.12.017. PMID:23274142[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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