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The first transmembrane region of complement component-9 acts as a brake on its self-assembly.
Spicer, Bradley A; Law, Ruby H P; Caradoc-Davies, Tom T; Ekkel, Sue M; Bayly-Jones, Charles; Pang, Siew-Siew; Conroy, Paul J; Ramm, Georg; Radjainia, Mazdak; Venugopal, Hariprasad; Whisstock, James C; Dunstone, Michelle A.
Afiliación
  • Spicer BA; ARC Centre of Excellence in Advanced Molecular Imaging, Department of Biochemistry and Molecular Biology, 23 Innovation Walk, Monash University, Victoria, 3800, Australia.
  • Law RHP; Biomedicine Discovery Institute, Department of Biochemistry and Molecular Biology, 23 Innovation Walk, Monash University, Victoria, 3800, Australia.
  • Caradoc-Davies TT; ARC Centre of Excellence in Advanced Molecular Imaging, Department of Biochemistry and Molecular Biology, 23 Innovation Walk, Monash University, Victoria, 3800, Australia.
  • Ekkel SM; Biomedicine Discovery Institute, Department of Biochemistry and Molecular Biology, 23 Innovation Walk, Monash University, Victoria, 3800, Australia.
  • Bayly-Jones C; ARC Centre of Excellence in Advanced Molecular Imaging, Department of Biochemistry and Molecular Biology, 23 Innovation Walk, Monash University, Victoria, 3800, Australia.
  • Pang SS; Australian Synchrotron, 800 Blackburn Road, Clayton, Victoria, 3168, Australia.
  • Conroy PJ; ARC Centre of Excellence in Advanced Molecular Imaging, Department of Biochemistry and Molecular Biology, 23 Innovation Walk, Monash University, Victoria, 3800, Australia.
  • Ramm G; Biomedicine Discovery Institute, Department of Biochemistry and Molecular Biology, 23 Innovation Walk, Monash University, Victoria, 3800, Australia.
  • Radjainia M; ARC Centre of Excellence in Advanced Molecular Imaging, Department of Biochemistry and Molecular Biology, 23 Innovation Walk, Monash University, Victoria, 3800, Australia.
  • Venugopal H; Biomedicine Discovery Institute, Department of Biochemistry and Molecular Biology, 23 Innovation Walk, Monash University, Victoria, 3800, Australia.
  • Whisstock JC; ARC Centre of Excellence in Advanced Molecular Imaging, Department of Biochemistry and Molecular Biology, 23 Innovation Walk, Monash University, Victoria, 3800, Australia.
  • Dunstone MA; Biomedicine Discovery Institute, Department of Biochemistry and Molecular Biology, 23 Innovation Walk, Monash University, Victoria, 3800, Australia.
Nat Commun ; 9(1): 3266, 2018 08 15.
Article en En | MEDLINE | ID: mdl-30111885
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 Å crystal structure of monomeric murine C9 and the 3.9 Å 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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Complemento C9 / Complejo de Ataque a Membrana del Sistema Complemento / Dominios Proteicos / Proteínas de la Membrana Límite: Animals / Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2018 Tipo del documento: Article País de afiliación: Australia Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Complemento C9 / Complejo de Ataque a Membrana del Sistema Complemento / Dominios Proteicos / Proteínas de la Membrana Límite: Animals / Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2018 Tipo del documento: Article País de afiliación: Australia Pais de publicación: Reino Unido