5HCE

Ternary complex of human Complement C5 with Ornithodoros moubata OmCI and Rhipicephalus appendiculatus RaCI1

5HCE の概要

• エントリーDOI: 10.2210/pdb5hce/pdb
• 分子名称: Complement C5, Complement inhibitor, Rhipicephalus appendiculatus RaCI1, ... (6 entities in total)
• 機能のキーワード: complement, inflammation, inhibitor, tick, immune system
• 由来する生物種: Ornithodoros moubata (Soft tick); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 213822.45

構造登録者

Jore, M.M.,Johnson, S.,Lea, S.M. (登録日: 2016-01-04, 公開日: 2016-03-30, 最終更新日: 2024-10-23)

主引用文献

Jore, M.M.,Johnson, S.,Sheppard, D.,Barber, N.M.,Li, Y.I.,Nunn, M.A.,Elmlund, H.,Lea, S.M.
Structural basis for therapeutic inhibition of complement C5.
Nat.Struct.Mol.Biol., 23:378-386, 2016

PubMed Abstract: Activation of complement C5 generates the potent anaphylatoxin C5a and leads to pathogen lysis, inflammation and cell damage. The therapeutic potential of C5 inhibition has been demonstrated by eculizumab, one of the world's most expensive drugs. However, the mechanism of C5 activation by C5 convertases remains elusive, thus limiting development of therapeutics. Here we identify and characterize a new protein family of tick-derived C5 inhibitors. Structures of C5 in complex with the new inhibitors, the phase I and phase II inhibitor OmCI, or an eculizumab Fab reveal three distinct binding sites on C5 that all prevent activation of C5. The positions of the inhibitor-binding sites and the ability of all three C5-inhibitor complexes to competitively inhibit the C5 convertase conflict with earlier steric-inhibition models, thus suggesting that a priming event is needed for activation.

PubMed: 27018802
DOI: 10.1038/nsmb.3196

実験手法

X-RAY DIFFRACTION (3.12 Å)