6DLW

Complement component polyC9

6DLW の概要

• エントリーDOI: 10.2210/pdb6dlw/pdb
• EMDBエントリー: 7773
• 分子名称: Complement component C9, 2-acetamido-2-deoxy-beta-D-glucopyranose, beta-D-mannopyranose (3 entities in total)
• 機能のキーワード: complement, pore, em, membrane, transmembrane, immune system
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 22
• 化学式量合計: 1352075.08

構造登録者

Dunstone, M.A.,Spicer, B.A.,Law, R.H.P. (登録日: 2018-06-03, 公開日: 2018-09-12, 最終更新日: 2024-10-23)

主引用文献

Spicer, B.A.,Law, R.H.P.,Caradoc-Davies, T.T.,Ekkel, S.M.,Bayly-Jones, C.,Pang, S.S.,Conroy, P.J.,Ramm, G.,Radjainia, M.,Venugopal, H.,Whisstock, J.C.,Dunstone, M.A.
The first transmembrane region of complement component-9 acts as a brake on its self-assembly.
Nat Commun, 9:3266-3266, 2018

PubMed Abstract: 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.

PubMed: 30111885
DOI: 10.1038/s41467-018-05717-0

実験手法

ELECTRON MICROSCOPY (3.9 Å)