2i6q
From Proteopedia
Complement component C2a
Structural highlights
DiseaseCO2_HUMAN Defects in C2 are the cause of complement component 2 deficiency (C2D) [MIM:217000. A deficiency of the complement classical pathway associated with the development of autoimmune disorders, mainly systemic lupus erythematosus. Skin and joint manifestations are common and renal disease is relatively rare. Patients with complement component 2 deficiency are also reported to have recurrent or invasive infections.[1] [2] FunctionCO2_HUMAN Component C2 which is part of the classical pathway of the complement system is cleaved by activated factor C1 into two fragments: C2b and C2a. C2a, a serine protease, then combines with complement factor 4b to generate the C3 or C5 convertase. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedC2a provides the catalytic center to the convertase complexes of the classical and lectin-binding pathways of complement activation. We determined two crystal structures of full-length C2a, with and without a pseudo ligand bound. Both structures reveal a near-active conformation of the catalytic center of the serine protease domains, while the von Willebrand factor A-type domains display an intermediate activation state of helix alpha7 with an open, activated metal-ion-dependent adhesion site. The open adhesion site likely serves to enhance the affinity for the ligand C4b, similar to "inside-out" signaling in integrins. Surprisingly, the N-terminal residues of C2a are buried in a crevice near helix alpha7, indicative of a structural switch between C2 and C2a. Extended loops on the protease domain possibly envelop the protruding anaphylatoxin domain of the substrate C3. Together with a putative substrate-induced completion of the oxyanion hole, this may contribute to the high substrate specificity of the convertases. Structure of complement component C2A: implications for convertase formation and substrate binding.,Milder FJ, Raaijmakers HC, Vandeputte MD, Schouten A, Huizinga EG, Romijn RA, Hemrika W, Roos A, Daha MR, Gros P Structure. 2006 Oct;14(10):1587-97. PMID:17027507[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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Categories: Homo sapiens | Large Structures | Daha MR | Gros P | Hemrika W | Huizinga EG | Milder FJ | Raaijmakers HCA | Romijn RA | Roos A | Schouten A | Vandeputte DAA
