6UY7

Crystal structure of the STAC3 tandem SH3 domains - P269R

6UY7 の概要

• エントリーDOI: 10.2210/pdb6uy7/pdb
• 分子名称: SH3 and cysteine-rich domain-containing protein 3, 1,2-ETHANEDIOL (3 entities in total)
• 機能のキーワード: protein binding domain, protein binding
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 14041.96

構造登録者

Rufenach, B.,Van Petegem, F. (登録日: 2019-11-12, 公開日: 2020-06-17, 最終更新日: 2023-10-11)

主引用文献

Rufenach, B.,Christy, D.,Flucher, B.E.,Bui, J.M.,Gsponer, J.,Campiglio, M.,Van Petegem, F.
Multiple Sequence Variants in STAC3 Affect Interactions with CaV1.1 and Excitation-Contraction Coupling.
Structure, 28:922-, 2020

PubMed Abstract: STAC3 is a soluble protein essential for skeletal muscle excitation-contraction (EC) coupling. Through its tandem SH3 domains, it interacts with the cytosolic II-III loop of the skeletal muscle voltage-gated calcium channel. STAC3 is the target for a mutation (W284S) that causes Native American myopathy, but multiple other sequence variants have been reported. Here, we report a crystal structure of the human STAC3 tandem SH3 domains. We analyzed the effect of five disease-associated variants, spread over both SH3 domains, on their ability to bind to the Ca1.1 II-III loop and on muscle EC coupling. In addition to W284S, we find the F295L and K329N variants to affect both binding and EC coupling. The ability of the K329N variant, located in the second SH3 domain, to affect the interaction highlights the importance of both SH3 domains in association with Ca1.1. Our results suggest that multiple STAC3 variants may cause myopathy.

PubMed: 32492370
DOI: 10.1016/j.str.2020.05.005

実験手法

X-RAY DIFFRACTION (2.105 Å)