5fmw
From Proteopedia
The poly-C9 component of the Complement Membrane Attack Complex
Structural highlights
DiseaseCO9_HUMAN Age-related macular degeneration;Immunodeficiency due to a late component of complements deficiency. Disease susceptibility is associated with variations affecting the gene represented in this entry. Disease susceptibility is associated with variations affecting the gene represented in this entry. FunctionCO9_HUMAN 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. Publication Abstract from PubMedThe membrane attack complex (MAC)/perforin-like protein complement component 9 (C9) is the major component of the MAC, a multi-protein complex that forms pores in the membrane of target pathogens. In contrast to homologous proteins such as perforin and the cholesterol-dependent cytolysins (CDCs), all of which require the membrane for oligomerisation, C9 assembles directly onto the nascent MAC from solution. However, the molecular mechanism of MAC assembly remains to be understood. Here we present the 8 A cryo-EM structure of a soluble form of the poly-C9 component of the MAC. These data reveal a 22-fold symmetrical arrangement of C9 molecules that yield an 88-strand pore-forming beta-barrel. The N-terminal thrombospondin-1 (TSP1) domain forms an unexpectedly extensive part of the oligomerisation interface, thus likely facilitating solution-based assembly. These TSP1 interactions may also explain how additional C9 subunits can be recruited to the growing MAC subsequent to membrane insertion. Structure of the poly-C9 component of the complement membrane attack complex.,Dudkina NV, Spicer BA, Reboul CF, Conroy PJ, Lukoyanova N, Elmlund H, Law RH, Ekkel SM, Kondos SC, Goode RJ, Ramm G, Whisstock JC, Saibil HR, Dunstone MA Nat Commun. 2016 Feb 4;7:10588. doi: 10.1038/ncomms10588. PMID:26841934[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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Categories: Homo sapiens | Large Structures | Conroy PJ | Dudkina NV | Dunstone MA | Ekkel SM | Elmlund H | Goode RJA | Kondos SC | Law RHP | Lukoyanova N | Ramm G | Reboul CF | Saibil HR | Spicer BA | Whisstock JC