8OQ3

Structure of methylamine treated human complement C3

8OQ3 の概要

• エントリーDOI: 10.2210/pdb8oq3/pdb
• EMDBエントリー: 17103
• 分子名称: Complement C3, nanobody hC3Nb1 with mutation, beta-D-mannopyranose-(1-4)-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: innate immune system, complement, activation, nanobody, immune system
• 由来する生物種: Lama glama; 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 400369.55

構造登録者

Gadeberg, T.A.F.,Andersen, G.R. (登録日: 2023-04-11, 公開日: 2024-02-21, 最終更新日: 2025-07-02)

主引用文献

Gadeberg, T.A.F.,Jorgensen, M.H.,Olesen, H.G.,Lorentzen, J.,Harwood, S.L.,Almeida, A.V.,Fruergaard, M.U.,Jensen, R.K.,Kanis, P.,Pedersen, H.,Tranchant, E.,Petersen, S.V.,Thogersen, I.B.,Kragelund, B.B.,Lyons, J.A.,Enghild, J.J.,Andersen, G.R.
Cryo-EM analysis of complement C3 reveals a reversible major opening of the macroglobulin ring.
Nat.Struct.Mol.Biol., 2025

PubMed Abstract: The C3 protein is the central molecule within the complement system and undergoes proteolytic activation to C3b in the presence of pathogens. Pattern-independent activation of C3 also occurs via hydrolysis, resulting in C3(HO), but the structural details of C3 hydrolysis remain elusive. Here we show that the conformation of the C3(HO) analog, C3MA, is indistinguishable from C3b. In contrast, the reaction intermediate C3* adopts a conformation dramatically different from both C3 and C3MA. In C3*, unlocking of the macroglobulin (MG) 3 domain creates a large opening in the MG ring through which the anaphylatoxin (ANA) domain translocates through a transient opening. C3MA formation is inhibited by an MG3-specific nanobody and prevented by linking the ANA domain to the C3 β-chain. Our study reveals an unexpected dynamic behavior of C3 and forms the basis for elucidation of the in vivo contribution of C3 hydrolysis and for controlling complement upon intravascular hemolysis and surface-contact-induced activation.

PubMed: 39849196
DOI: 10.1038/s41594-024-01467-4

実験手法

ELECTRON MICROSCOPY (2.9 Å)