4ONT

Ternary host recognition complex of complement factor H, C3d, and sialic acid

4ONT の概要

• エントリーDOI: 10.2210/pdb4ont/pdb
• 分子名称: Complement factor H, Complement C3d fragment, N-acetyl-alpha-neuraminic acid-(2-3)-beta-D-galactopyranose-(1-4)-beta-D-glucopyranose, ... (5 entities in total)
• 機能のキーワード: complement control protein, ccp, short consensus repeat, scr, sushi domain, complement regulation, sialic acid, host glycan, host cell surface, immune system
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Secreted: P08603 P01024
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 153200.01

構造登録者

Blaum, B.S.,Stehle, T.S. (登録日: 2014-01-29, 公開日: 2014-11-26, 最終更新日: 2024-11-20)

主引用文献

Blaum, B.S.,Hannan, J.P.,Herbert, A.P.,Kavanagh, D.,Uhrin, D.,Stehle, T.
Structural basis for sialic acid-mediated self-recognition by complement factor H.
Nat.Chem.Biol., 11:77-82, 2015

PubMed Abstract: The serum protein complement factor H (FH) ensures downregulation of the complement alternative pathway, a branch of innate immunity, upon interaction with specific glycans on host cell surfaces. Using ligand-based NMR, we screened a comprehensive set of sialylated glycans for binding to FH and solved the crystal structure of a ternary complex formed by the two C-terminal domains of FH, a sialylated trisaccharide and the complement C3b thioester-containing domain. Key residues in the sialic acid binding site are conserved from mice to men, and residues linked to atypical hemolytic uremic syndrome cluster within this binding site, suggesting a possible role for sialic acid as a host marker also in other mammals and a critical role in human renal complement homeostasis. Unexpectedly, the FH sialic acid binding site is structurally homologous to the binding sites of two evolutionarily unrelated proteins. The crystal structure also advances our understanding of bacterial immune evasion strategies.

PubMed: 25402769
DOI: 10.1038/nchembio.1696

実験手法

X-RAY DIFFRACTION (2.15 Å)