6CHF

Crystal structure of a Fc fragment LALA mutant (L234A, L235A) of human IgG1 (crystal form 1)

6CHF の概要

• エントリーDOI: 10.2210/pdb6chf/pdb
• 分子名称: Uncharacterized protein DKFZp686C11235, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-[2-acetamido-2-deoxy-beta-D-glucopyranose-(1-2)-alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[alpha-L-fucopyranose-(1-6)]2-acetamido-2-deoxy-beta-D-glucopyranose (3 entities in total)
• 機能のキーワード: immunoglobulin, igg1, immune system, immunoglobulin-like beta sandwich, fc fragment, lala mutation
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 51225.28

構造登録者

Gohain, N.,Tolbert, W.D.,Pazgier, M. (登録日: 2018-02-22, 公開日: 2019-02-27, 最終更新日: 2024-11-20)

主引用文献

Orlandi, C.,Deredge, D.,Ray, K.,Gohain, N.,Tolbert, W.,DeVico, A.L.,Wintrode, P.,Pazgier, M.,Lewis, G.K.
Antigen-Induced Allosteric Changes in a Human IgG1 Fc Increase Low-Affinity Fc gamma Receptor Binding.
Structure, 2020

PubMed Abstract: Antibody structure couples adaptive and innate immunity via Fab (antigen binding) and Fc (effector) domains that are connected by unique hinge regions. Because antibodies harbor two or more Fab domains, they are capable of crosslinking multi-determinant antigens, which is required for Fc-dependent functions through associative interactions with effector ligands, including C1q and cell surface Fc receptors. The modular nature of antibodies, with distal ligand binding sites for antigen and Fc-ligands, is reminiscent of allosteric proteins, suggesting that allosteric interactions might contribute to Fc-mediated effector functions. This hypothesis has been pursued for over 40 years and remains unresolved. Here, we provide evidence that allosteric interactions between Fab and Fc triggered by antigen binding modulate binding of Fc to low-affinity Fc receptors (FcγR) for a human IgG1. This work opens the path to further dissection of the relative roles of allosteric and associative interactions in Fc-mediated effector functions.

PubMed: 32209433
DOI: 10.1016/j.str.2020.03.001

実験手法

X-RAY DIFFRACTION (2.4 Å)