4A5W

Crystal structure of C5b6

4A5W の概要

• エントリーDOI: 10.2210/pdb4a5w/pdb
• 関連するPDBエントリー: 1CFA 1KJS 1XWE
• EMDBエントリー: 1991
• 分子名称: COMPLEMENT C5, COMPLEMENT COMPONENT C6, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (6 entities in total)
• 機能のキーワード: immune system, immunity, membrane attack complex
• 由来する生物種: HOMO SAPIENS (HUMAN); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 281878.24

構造登録者

Hadders, M.A.,Bubeck, D.,Forneris, F.,Pangburn, M.,Llorca, O.,Lea, S.M.,Gros, P. (登録日: 2011-10-28, 公開日: 2012-03-14, 最終更新日: 2024-07-24)

主引用文献

Hadders, M.A.,Bubeck, D.,Roversi, P.,Hakobyan, S.,Forneris, F.,Morgan, B.P.,Pangburn, M.K.,Llorca, O.,Lea, S.M.,Gros, P.
Assembly and Regulation of the Membrane Attack Complex Based on Structures of C5B6 and Sc5B9.
Cell Rep., 1:200-, 2012

PubMed Abstract: Activation of the complement system results in formation of membrane attack complexes (MACs), pores that disrupt lipid bilayers and lyse bacteria and other pathogens. Here, we present the crystal structure of the first assembly intermediate, C5b6, together with a cryo-electron microscopy reconstruction of a soluble, regulated form of the pore, sC5b9. Cleavage of C5 to C5b results in marked conformational changes, distinct from those observed in the homologous C3-to-C3b transition. C6 captures this conformation, which is preserved in the larger sC5b9 assembly. Together with antibody labeling, these structures reveal that complement components associate through sideways alignment of the central MAC-perforin (MACPF) domains, resulting in a C5b6-C7-C8β-C8α-C9 arc. Soluble regulatory proteins below the arc indicate a potential dual mechanism in protection from pore formation. These results provide a structural framework for understanding MAC pore formation and regulation, processes important for fighting infections and preventing complement-mediated tissue damage.

PubMed: 22832194
DOI: 10.1016/J.CELREP.2012.02.003

実験手法

X-RAY DIFFRACTION (3.5 Å)