4UMO

Crystal Structure of the Kv7.1 proximal C-terminal Domain in Complex with Calmodulin

4UMO の概要

• エントリーDOI: 10.2210/pdb4umo/pdb
• 分子名称: POTASSIUM VOLTAGE-GATED CHANNEL SUBFAMILY KQT MEMBER 1, CALMODULIN, POTASSIUM ION, ... (6 entities in total)
• 機能のキーワード: signaling protein, long qt syndrome
• 由来する生物種: HOMO SAPIENS (HUMAN); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 60956.26

構造登録者

Sachyani, D.,Hirsch, J.A. (登録日: 2014-05-20, 公開日: 2014-11-05, 最終更新日: 2024-05-08)

主引用文献

Sachyani, D.,Dvir, M.,Strulovich, R.,Tria, G.,Tobelaim, W.,Peretz, A.,Pongs, O.,Svergun, D.,Attali, B.,Hirsch, J.A.
Structural Basis of a Kv7.1 Potassium Channel Gating Module: Studies of the Intracellular C-Terminal Domain in Complex with Calmodulin
Structure, 22:1582-, 2014

PubMed Abstract: Kv7 channels tune neuronal and cardiomyocyte excitability. In addition to the channel membrane domain, they also have a unique intracellular C-terminal (CT) domain, bound constitutively to calmodulin (CaM). This CT domain regulates gating and tetramerization. We investigated the structure of the membrane proximal CT module in complex with CaM by X-ray crystallography. The results show how the CaM intimately hugs a two-helical bundle, explaining many channelopathic mutations. Structure-based mutagenesis of this module in the context of concatemeric tetramer channels and functional analysis along with in vitro data lead us to propose that one CaM binds to one individual protomer, without crosslinking subunits and that this configuration is required for proper channel expression and function. Molecular modeling of the CT/CaM complex in conjunction with small-angle X-ray scattering suggests that the membrane proximal region, having a rigid lever arm, is a critical gating regulator.

PubMed: 25441029
DOI: 10.1016/J.STR.2014.07.016

実験手法

X-RAY DIFFRACTION (3 Å)