5HIT

Crystal Structure Analysis of Ca2+-calmodulin and a C-terminal EAG1 channel fragment

5HIT の概要

• エントリーDOI: 10.2210/pdb5hit/pdb
• 分子名称: Calmodulin, Potassium voltage-gated channel subfamily H member 1, CALCIUM ION, ... (4 entities in total)
• 機能のキーワード: calmodulin, potassium channel, signaling protein
• 由来する生物種: Gallus gallus (Chicken); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 18701.76

構造登録者

Marques-Carvalho, M.J.,Morais-Cabral, J.H. (登録日: 2016-01-12, 公開日: 2016-09-14, 最終更新日: 2024-01-10)

主引用文献

Marques-Carvalho, M.J.,Oppermann, J.,Munoz, E.,Fernandes, A.S.,Gabant, G.,Cadene, M.,Heinemann, S.H.,Schonherr, R.,Morais-Cabral, J.H.
Molecular Insights into the Mechanism of Calmodulin Inhibition of the EAG1 Potassium Channel.
Structure, 24:1742-1754, 2016

PubMed Abstract: The human EAG1 potassium channel belongs to the superfamily of KCNH voltage-gated potassium channels that have roles in cardiac repolarization and neuronal excitability. EAG1 is strongly inhibited by Ca/calmodulin (CaM) through a mechanism that is not understood. We determined the binding properties of CaM with each one of three previously identified binding sites (BDN, BDC1, and BDC2), analyzed binding to protein stretches that include more than one site, and determined the effect of neighboring globular domains on the binding properties. The determination of the crystal structure of CaM bound to BDC2 shows the channel fragment interacting with only the C lobe of calmodulin and adopting an unusual bent conformation. Based on this structure and on a functional and biochemical analysis of mutants, we propose a model for the mechanism of inhibition whereby the local conformational change induced by CaM binding at BDC2 lies at the basis of channel modulation.

PubMed: 27618660
DOI: 10.1016/j.str.2016.07.020

実験手法

X-RAY DIFFRACTION (2.85 Å)