3V8C

Crystal structure of monoclonal human anti-rhesus D Fc IgG1 t125(yb2/0) double mutant (H310 and H435 in K)

3V8C の概要

• エントリーDOI: 10.2210/pdb3v8c/pdb
• 関連するPDBエントリー: 2J6E 3FJT 3V7M
• 分子名称: Ig gamma-1 chain C region, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-2)-alpha-D-mannopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (7 entities in total)
• 機能のキーワード: fc igg1, fc-gamma receptor, immune system
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Secreted: P01857
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 51383.46

構造登録者

Menez, R.,Stura, E.A.,Bourel, D.,Siberil, S.,Jorieux, S.,De Romeuf, C.,Ducancel, F.,Fridman, W.H.,Teillaud, J.L. (登録日: 2011-12-22, 公開日: 2012-02-22, 最終更新日: 2024-11-20)

主引用文献

Siberil, S.,Menez, R.,Jorieux, S.,de Romeuf, C.,Bourel, D.,Fridman, W.H.,Ducancel, F.,Stura, E.A.,Teillaud, J.L.
Effect of zinc on human IgG1 and its Fc gamma R interactions.
Immunol.Lett., 143:60-69, 2012

PubMed Abstract: In the present study, we show that histidines 310 and 435 at the CH2-CH3 interface of the Fc portion of human IgG1 can coordinate a Zn2+ and participate in the control of the CH2-CH2 interdomain opening. Structures obtained in the absence of Zn2+ have a reduced interdomain gap that likely hamper FcγR binding. This closed conformation of the Fc is stabilized by inter-CH2 domain sugar contacts. Zinc appears to counteract the sugar mediated constriction, suggesting that zinc could be an important control factor in IgG1/FcγR interactions. The results of binding studies performed in the presence of EDTA on FcγR expressing cells supports this hypothesis. When a mutated Fc fragment, in which histidines 310 and 435 have been substituted by lysines (Fc H/K), was compared with the wild-type Fc in crystallographic studies, we found that the mutations leave the interface unaltered but have a long-range effect on the CH2 interdomain separation. Moreover, these substitutions have a differential effect on the binding of IgG1 to Fcγ receptors and their functions. Interaction with the inhibitory FcγRIIB is strongly perturbed by the mutations and mutant IgG1 H/K only weakly engages this receptor. By contrast, higher affinity FcγR are mostly unaffected.

PubMed: 22553781

実験手法

X-RAY DIFFRACTION (2.77 Å)