5FMW

The poly-C9 component of the Complement Membrane Attack Complex

Summary for 5FMW

• Entry DOI: 10.2210/pdb5fmw/pdb
• EMDB information: 3235
• Descriptor: POLYC9 (1 entity in total)
• Functional Keywords: structural protein, pore-forming protein, complement, c9, macpf
• Biological source: HOMO SAPIENS (HUMAN)
• Cellular location: Secreted : P02748
• Total number of polymer chains: 22
• Total formula weight: 1266823.16

Authors

Dudkina, N.V.,Spicer, B.A.,Reboul, C.F.,Conroy, P.J.,Lukoyanova, N.,Elmlund, H.,Law, R.H.P.,Ekkel, S.M.,Kondos, S.C.,Goode, R.J.A.,Ramm, G.,Whisstock, J.C.,Saibil, H.R.,Dunstone, M.A. (deposition date: 2015-11-10, release date: 2016-02-17, Last modification date: 2024-05-08)

Primary citation

Dudkina, N.V.,Spicer, B.A.,Reboul, C.F.,Conroy, P.J.,Lukoyanova, N.,Elmlund, H.,Law, R.H.P.,Ekkel, S.M.,Kondos, S.C.,Goode, R.J.A.,Ramm, G.,Whisstock, J.C.,Saibil, H.R.,Dunstone, M.A.
Structure of the Poly-C9 Component of the Complement Membrane Attack Complex
Nat.Commun., 7:10588-, 2016

PubMed Abstract: The 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 Å 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 β-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.

PubMed: 26841934
DOI: 10.1038/NCOMMS10588

Experimental method

ELECTRON MICROSCOPY (6.7 Å)