5HBV

Complex structure of Fab35 and mouse nAChR alpha1

5HBV の概要

• エントリーDOI: 10.2210/pdb5hbv/pdb
• 関連するPDBエントリー: 5HBT
• 分子名称: Alpha-bungarotoxin isoform V31, Acetylcholine receptor subunit alpha 1, Fab35, Light Chain, ... (6 entities in total)
• 機能のキーワード: nicotinic acetylcholine receptor alpha1, fab35, complex, myasthenia gravis, transport protein-toxin complex, transport protein/toxin
• 由来する生物種: Mus musculus (Mouse); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 81594.47

構造登録者

Noridomi, K.,Watanabe, G.,Hansen, M.N.,Han, G.W.,Chen, L. (登録日: 2016-01-02, 公開日: 2017-05-03, 最終更新日: 2024-10-09)

主引用文献

Noridomi, K.,Watanabe, G.,Hansen, M.N.,Han, G.W.,Chen, L.
Structural insights into the molecular mechanisms of myasthenia gravis and their therapeutic implications.
Elife, 6:-, 2017

PubMed Abstract: The nicotinic acetylcholine receptor (nAChR) is a major target of autoantibodies in myasthenia gravis (MG), an autoimmune disease that causes neuromuscular transmission dysfunction. Despite decades of research, the molecular mechanisms underlying MG have not been fully elucidated. Here, we present the crystal structure of the nAChR α1 subunit bound by the Fab fragment of mAb35, a reference monoclonal antibody that causes experimental MG and competes with ~65% of antibodies from MG patients. Our structures reveal for the first time the detailed molecular interactions between MG antibodies and a core region on nAChR α1. These structures suggest a major nAChR-binding mechanism shared by a large number of MG antibodies and the possibility to treat MG by blocking this binding mechanism. Structure-based modeling also provides insights into antibody-mediated nAChR cross-linking known to cause receptor degradation. Our studies establish a structural basis for further mechanistic studies and therapeutic development of MG.

PubMed: 28440223
DOI: 10.7554/eLife.23043

実験手法

X-RAY DIFFRACTION (2.7 Å)