title: Structure of the poly-C9 component of the complement membrane attack complex.
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.
authors: Department of Crystallography, Institute of Structural and Molecular Biology, Birkbeck College, London WC1E 7HX, UK.
authors: Natalya V
authors: NV
authors: Dudkina
authors: ARC Centre of Excellence in Advanced Molecular Imaging, Clayton Campus, Monash University, Melbourne, Victoria 3800, Australia.|Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Clayton Campus, Monash University, Melbourne, Victoria 3800, Australia.
authors: Bradley A
authors: BA
authors: Spicer
authors: ARC Centre of Excellence in Advanced Molecular Imaging, Clayton Campus, Monash University, Melbourne, Victoria 3800, Australia.|Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Clayton Campus, Monash University, Melbourne, Victoria 3800, Australia.
authors: Cyril F
authors: CF
authors: Reboul
authors: ARC Centre of Excellence in Advanced Molecular Imaging, Clayton Campus, Monash University, Melbourne, Victoria 3800, Australia.|Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Clayton Campus, Monash University, Melbourne, Victoria 3800, Australia.
authors: Paul J
authors: PJ
authors: Conroy
authors: Department of Crystallography, Institute of Structural and Molecular Biology, Birkbeck College, London WC1E 7HX, UK.
authors: Natalya
authors: N
authors: Lukoyanova
authors: ARC Centre of Excellence in Advanced Molecular Imaging, Clayton Campus, Monash University, Melbourne, Victoria 3800, Australia.|Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Clayton Campus, Monash University, Melbourne, Victoria 3800, Australia.
authors: Hans
authors: H
authors: Elmlund
authors: ARC Centre of Excellence in Advanced Molecular Imaging, Clayton Campus, Monash University, Melbourne, Victoria 3800, Australia.|Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Clayton Campus, Monash University, Melbourne, Victoria 3800, Australia.
authors: Ruby H P
authors: RH
authors: Law
authors: ARC Centre of Excellence in Advanced Molecular Imaging, Clayton Campus, Monash University, Melbourne, Victoria 3800, Australia.|Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Clayton Campus, Monash University, Melbourne, Victoria 3800, Australia.
authors: Susan M
authors: SM
authors: Ekkel
authors: Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Clayton Campus, Monash University, Melbourne, Victoria 3800, Australia.
authors: Stephanie C
authors: SC
authors: Kondos
authors: Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Clayton Campus, Monash University, Melbourne, Victoria 3800, Australia.
authors: Robert J A
authors: RJ
authors: Goode
authors: ARC Centre of Excellence in Advanced Molecular Imaging, Clayton Campus, Monash University, Melbourne, Victoria 3800, Australia.|Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Clayton Campus, Monash University, Melbourne, Victoria 3800, Australia.
authors: Georg
authors: G
authors: Ramm
authors: ARC Centre of Excellence in Advanced Molecular Imaging, Clayton Campus, Monash University, Melbourne, Victoria 3800, Australia.|Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Clayton Campus, Monash University, Melbourne, Victoria 3800, Australia.
authors: James C
authors: JC
authors: Whisstock
authors: Department of Crystallography, Institute of Structural and Molecular Biology, Birkbeck College, London WC1E 7HX, UK.
authors: Helen R
authors: HR
authors: Saibil
authors: ARC Centre of Excellence in Advanced Molecular Imaging, Clayton Campus, Monash University, Melbourne, Victoria 3800, Australia.|Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Clayton Campus, Monash University, Melbourne, Victoria 3800, Australia.|Department of Microbiology, Biomedicine Discovery Institute, Clayton Campus, Monash University, Melbourne, 3800 Victoria, Australia.
authors: Michelle A
authors: MA
authors: Dunstone
mesh_terms: D003186:Complement C9 / Q000648:ultrastructure*; D015938:Complement Membrane Attack Complex / Q000648:ultrastructure*; D020285:Cryoelectron Microscopy; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D011108:Polymers
chemical_list: D003186:Complement C9; D015938:Complement Membrane Attack Complex; D011108:Polymers