5O35

Structure of complement proteins complex

5O35 の概要

• エントリーDOI: 10.2210/pdb5o35/pdb
• 分子名称: Complement C3, Complement factor H,Complement factor H, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (4 entities in total)
• 機能のキーワード: complement, regulation, complex, immune system
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 218685.98

構造登録者

Xue, X.,Wu, J.,Forneris, F.,Gros, P. (登録日: 2017-05-23, 公開日: 2017-06-28, 最終更新日: 2024-11-06)

主引用文献

Xue, X.,Wu, J.,Ricklin, D.,Forneris, F.,Di Crescenzio, P.,Schmidt, C.Q.,Granneman, J.,Sharp, T.H.,Lambris, J.D.,Gros, P.
Regulator-dependent mechanisms of C3b processing by factor I allow differentiation of immune responses.
Nat. Struct. Mol. Biol., 24:643-651, 2017

PubMed Abstract: The complement system labels microbes and host debris for clearance. Degradation of surface-bound C3b is pivotal to direct immune responses and protect host cells. How the serine protease factor I (FI), assisted by regulators, cleaves either two or three distant peptide bonds in the CUB domain of C3b remains unclear. We present a crystal structure of C3b in complex with FI and regulator factor H (FH; domains 1-4 with 19-20). FI binds C3b-FH between FH domains 2 and 3 and a reoriented C3b C-terminal domain and docks onto the first scissile bond, while stabilizing its catalytic domain for proteolytic activity. One cleavage in C3b does not affect its overall structure, whereas two cleavages unfold CUB and dislodge the thioester-containing domain (TED), affecting binding of regulators and thereby determining the number of cleavages. These data explain how FI generates late-stage opsonins iC3b or C3dg in a context-dependent manner, to react to foreign, danger or healthy self signals.

PubMed: 28671664
DOI: 10.1038/nsmb.3427

実験手法

X-RAY DIFFRACTION (4.2 Å)