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-Structure paper
タイトル | Structural basis of complement membrane attack complex formation. |
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ジャーナル・号・ページ | Nat Commun, Vol. 7, Page 10587, Year 2016 |
掲載日 | 2016年2月4日 |
著者 | Marina Serna / Joanna L Giles / B Paul Morgan / Doryen Bubeck / |
PubMed 要旨 | In response to complement activation, the membrane attack complex (MAC) assembles from fluid-phase proteins to form pores in lipid bilayers. MAC directly lyses pathogens by a 'multi-hit' mechanism; ...In response to complement activation, the membrane attack complex (MAC) assembles from fluid-phase proteins to form pores in lipid bilayers. MAC directly lyses pathogens by a 'multi-hit' mechanism; however, sublytic MAC pores on host cells activate signalling pathways. Previous studies have described the structures of individual MAC components and subcomplexes; however, the molecular details of its assembly and mechanism of action remain unresolved. Here we report the electron cryo-microscopy structure of human MAC at subnanometre resolution. Structural analyses define the stoichiometry of the complete pore and identify a network of interaction interfaces that determine its assembly mechanism. MAC adopts a 'split-washer' configuration, in contrast to the predicted closed ring observed for perforin and cholesterol-dependent cytolysins. Assembly precursors partially penetrate the lipid bilayer, resulting in an irregular β-barrel pore. Our results demonstrate how differences in symmetric and asymmetric components of the MAC underpin a molecular basis for pore formation and suggest a mechanism of action that extends beyond membrane penetration. |
リンク | Nat Commun / PubMed:26841837 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 7.3 - 8.5 Å |
構造データ | EMDB-3134: EMDB-3135: |
由来 |
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