4ZH1

Complement factor H in complex with the GM1 glycan

4ZH1 の概要

• エントリーDOI: 10.2210/pdb4zh1/pdb
• 分子名称: Complement C3, Complement factor H, N-acetyl-alpha-neuraminic acid-(2-3)-beta-D-galactopyranose, ... (7 entities in total)
• 機能のキーワード: lectin, ganglioside, innate immunity, glycans, immune system
• 由来する生物種: Homo sapiens (Human); 詳細
• 細胞内の位置: Secreted: P01024 P08603
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 153330.11

構造登録者

Blaum, B.S.,Stehle, T. (登録日: 2015-04-24, 公開日: 2016-01-13, 最終更新日: 2024-11-20)

主引用文献

Blaum, B.S.,Frank, M.,Walker, R.C.,Neu, U.,Stehle, T.
Complement Factor H and Simian Virus 40 bind the GM1 ganglioside in distinct conformations.
Glycobiology, 26:532-539, 2016

PubMed Abstract: Mammalian cell surfaces are decorated with a variety of glycan chains that orchestrate development and defense and are exploited by pathogens for cellular attachment and entry. While glycosidic linkages are, in principle, flexible, the conformational space that a given glycan can sample is subject to spatial and electrostatic restrictions imposed by its overall chemical structure. Here, we show how the glycan moiety of the GM1 ganglioside, a branched, monosialylated pentasaccharide that serves as a ligand for various proteins, undergoes differential conformational selection in its interactions with different lectins. Using STD NMR and X-ray crystallography, we found that the innate immune regulator complement Factor H (FH) binds a previously not reported GM1 conformation that is not compatible with the GM1-binding sites of other structurally characterized GM1-binding lectins such as the Simian Virus 40 (SV40) capsid. Molecular dynamics simulations of the free glycan in explicit solvent on the 10 μs timescale reveal that the FH-bound conformation nevertheless corresponds to a minimum in the Gibbs free energy plot. In contrast to the GM1 conformation recognized by SV40, the FH-bound GM1 conformation is associated with poor NOE restraints, explaining how it escaped(1)H-(1)H NOE-restrained modeling in the past and highlighting the necessity for ensemble representations of glycan structures.

PubMed: 26715202
DOI: 10.1093/glycob/cwv170

実験手法

X-RAY DIFFRACTION (2.24 Å)