5VMS

CryoEM structure of Xenopus KCNQ1 channel

5VMS の概要

• エントリーDOI: 10.2210/pdb5vms/pdb
• EMDBエントリー: 8712
• 分子名称: Potassium voltage-gated channel subfamily KQT member 1, Calmodulin, CALCIUM ION (3 entities in total)
• 機能のキーワード: kcnq1-cam complex, potassium channel, long qt syndrome, transport protein, calcium binding protein
• 由来する生物種: Xenopus laevis (African clawed frog); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 79636.18

構造登録者

Mackinnon, R.,Sun, J. (登録日: 2017-04-28, 公開日: 2017-06-07, 最終更新日: 2024-03-13)

主引用文献

Sun, J.,MacKinnon, R.
Cryo-EM Structure of a KCNQ1/CaM Complex Reveals Insights into Congenital Long QT Syndrome.
Cell, 169:1042-1050.e9, 2017

PubMed Abstract: KCNQ1 is the pore-forming subunit of cardiac slow-delayed rectifier potassium (I) channels. Mutations in the kcnq1 gene are the leading cause of congenital long QT syndrome (LQTS). Here, we present the cryoelectron microscopy (cryo-EM) structure of a KCNQ1/calmodulin (CaM) complex. The conformation corresponds to an "uncoupled," PIP-free state of KCNQ1, with activated voltage sensors and a closed pore. Unique structural features within the S4-S5 linker permit uncoupling of the voltage sensor from the pore in the absence of PIP. CaM contacts the KCNQ1 voltage sensor through a specific interface involving a residue on CaM that is mutated in a form of inherited LQTS. Using an electrophysiological assay, we find that this mutation on CaM shifts the KCNQ1 voltage-activation curve. This study describes one physiological form of KCNQ1, depolarized voltage sensors with a closed pore in the absence of PIP, and reveals a regulatory interaction between CaM and KCNQ1 that may explain CaM-mediated LQTS.

PubMed: 28575668
DOI: 10.1016/j.cell.2017.05.019

実験手法

ELECTRON MICROSCOPY (3.7 Å)