2qki

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spinqualitylabelsall models 2qki, resolution 2.40Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

Human C3c in complex with the inhibitor compstatin

Overview

Undesired complement activation is a major cause of tissue injury in, various pathological conditions and contributes to several immune complex, diseases. Compstatin, a 13-residue peptide, is an effective inhibitor of, the activation of complement component C3 and thus blocks a central and, crucial step in the complement cascade. The precise binding site on C3, the structure in the bound form, and the exact mode of action of, compstatin are unknown. Here we present the crystal structure of, compstatin in complex with C3c, a major proteolytic fragment of C3. The, structure reveals that the compstatin-binding site is formed by the, macroglobulin (MG) domains 4 and 5. This binding site is part of the, structurally stable MG-ring formed by domains MG 1-6 and is far away from, any other known binding site on C3. Compstatin does not alter the, conformation of C3c, whereas compstatin itself undergoes a large, conformational change upon binding. We propose a model in which compstatin, sterically hinders the access of the substrate C3 to the convertase, complexes, thus blocking complement activation and amplification. These, insights are instrumental for further development of compstatin as a, potential therapeutic.

About this Structure

2QKI is a Protein complex structure of sequences from Homo sapiens with , , , and as ligands. Full crystallographic information is available from OCA.

Reference

Structure of compstatin in complex with complement component C3c reveals a new mechanism of complement inhibition., Janssen BJ, Halff EF, Lambris JD, Gros P, J Biol Chem. 2007 Oct 5;282(40):29241-7. Epub 2007 Aug 6. PMID:17684013

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