2QKI
Human C3c in complex with the inhibitor compstatin
Summary for 2QKI
| Entry DOI | 10.2210/pdb2qki/pdb |
| Related | 1A1P 2A73 2A74 2I07 2ICE 2ICF |
| Descriptor | Complement C3, compstatin, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (9 entities in total) |
| Functional Keywords | immunity, complement inhibitor design, c3, compstatin, immune system-hydrolase inhibitor complex, immune system/hydrolase inhibitor |
| Biological source | Homo sapiens (human) More |
| Cellular location | Secreted: P01024 P01024 P01024 |
| Total number of polymer chains | 8 |
| Total formula weight | 273113.36 |
| Authors | Janssen, B.J.C.,Halff, E.F.,Lambris, J.D.,Gros, P. (deposition date: 2007-07-11, release date: 2007-08-14, Last modification date: 2024-11-13) |
| Primary citation | Janssen, B.J.,Halff, E.F.,Lambris, J.D.,Gros, P. Structure of compstatin in complex with complement component C3c reveals a new mechanism of complement inhibition. J.Biol.Chem., 282:29241-29247, 2007 Cited by PubMed Abstract: 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. PubMed: 17684013DOI: 10.1074/jbc.M704587200 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.4 Å) |
Structure validation
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