7NYD

cryoEM structure of 2C9-sMAC

これはPDB形式変換不可エントリーです。

7NYD の概要

• エントリーDOI: 10.2210/pdb7nyd/pdb
• 関連するPDBエントリー: 7NYC
• EMDBエントリー: 12646 12647 12648 12649 12650 12651
• 分子名称: Complement component C8 beta chain, alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, alpha-D-mannopyranose, ... (14 entities in total)
• 機能のキーワード: complement, macpf, membrane attack complex, cdc, pore forming, immune system
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 649729.38

構造登録者

Menny, A.,Couves, E.C.,Bubeck, D. (登録日: 2021-03-22, 公開日: 2021-10-06, 最終更新日: 2024-11-06)

主引用文献

Menny, A.,Lukassen, M.V.,Couves, E.C.,Franc, V.,Heck, A.J.R.,Bubeck, D.
Structural basis of soluble membrane attack complex packaging for clearance.
Nat Commun, 12:6086-6086, 2021

PubMed Abstract: Unregulated complement activation causes inflammatory and immunological pathologies with consequences for human disease. To prevent bystander damage during an immune response, extracellular chaperones (clusterin and vitronectin) capture and clear soluble precursors to the membrane attack complex (sMAC). However, how these chaperones block further polymerization of MAC and prevent the complex from binding target membranes remains unclear. Here, we address that question by combining cryo electron microscopy (cryoEM) and cross-linking mass spectrometry (XL-MS) to solve the structure of sMAC. Together our data reveal how clusterin recognizes and inhibits polymerizing complement proteins by binding a negatively charged surface of sMAC. Furthermore, we show that the pore-forming C9 protein is trapped in an intermediate conformation whereby only one of its two transmembrane β-hairpins has unfurled. This structure provides molecular details for immune pore formation and helps explain a complement control mechanism that has potential implications for how cell clearance pathways mediate immune homeostasis.

PubMed: 34667172
DOI: 10.1038/s41467-021-26366-w

実験手法

ELECTRON MICROSCOPY (3.27 Å)