6cxo | pdb_00006cxo

Complement component-9

spinqualitylabelsall models 6cxo, resolution 2.20Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6cxo is a 2 chain structure with sequence from Lk3 transgenic mice. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: BMA, CA, MG, NAG, ZN Gene: C9 (LK3 transgenic mice) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [CO9_MOUSE] Constituent of the membrane attack complex (MAC) that plays a key role in the innate and adaptive immune response by forming pores in the plasma membrane of target cells. C9 is the pore-forming subunit of the MAC.[UniProtKB:P02748] Publication Abstract from PubMed Complement component 9 (C9) functions as the pore-forming component of the Membrane Attack Complex (MAC). During MAC assembly, multiple copies of C9 are sequentially recruited to membrane associated C5b8 to form a pore. Here we determined the 2.2 A crystal structure of monomeric murine C9 and the 3.9 A resolution cryo EM structure of C9 in a polymeric assembly. Comparison with other MAC proteins reveals that the first transmembrane region (TMH1) in monomeric C9 is uniquely positioned and functions to inhibit its self-assembly in the absence of C5b8. We further show that following C9 recruitment to C5b8, a conformational change in TMH1 permits unidirectional and sequential binding of additional C9 monomers to the growing MAC. This mechanism of pore formation contrasts with related proteins, such as perforin and the cholesterol dependent cytolysins, where it is believed that pre-pore assembly occurs prior to the simultaneous release of the transmembrane regions. The first transmembrane region of complement component-9 acts as a brake on its self-assembly.,Spicer BA, Law RHP, Caradoc-Davies TT, Ekkel SM, Bayly-Jones C, Pang SS, Conroy PJ, Ramm G, Radjainia M, Venugopal H, Whisstock JC, Dunstone MA Nat Commun. 2018 Aug 15;9(1):3266. doi: 10.1038/s41467-018-05717-0. PMID:30111885 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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