5J03

Crystal Structure of a chimeric Kv7.2 - Kv7.3 proximal C-terminal Domain in Complex with Calmodulin

5J03 の概要

• エントリーDOI: 10.2210/pdb5j03/pdb
• 関連するPDBエントリー: 4umo 4v0c
• 分子名称: Potassium voltage-gated channel subfamily KQT member 3,Potassium voltage-gated channel subfamily KQT member 2, Calmodulin, CALCIUM ION, ... (5 entities in total)
• 機能のキーワード: voltage-gated potassium channel, complex, calmodulin, transport protein
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 30178.86

構造登録者

Strulovich, R.,Hirsch, J.A. (登録日: 2016-03-26, 公開日: 2016-09-07, 最終更新日: 2024-05-08)

主引用文献

Strulovich, R.,Tobelaim, W.S.,Attali, B.,Hirsch, J.A.
Structural Insights into the M-Channel Proximal C-Terminus/Calmodulin Complex.
Biochemistry, 55:5353-5365, 2016

PubMed Abstract: The Kv7 (KCNQ) channel family, comprising voltage-gated potassium channels, plays major roles in fine-tuning cellular excitability by reducing firing frequency and controlling repolarization. Kv7 channels have a unique intracellular C-terminal (CT) domain bound constitutively by calmodulin (CaM). This domain plays key functions in channel tetramerization, trafficking, and gating. CaM binds to the proximal CT, comprising helices A and B. Kv7.2 and Kv7.3 are expressed in neural tissues. Together, they form the heterotetrameric M channel. We characterized Kv7.2, Kv7.3, and chimeric Kv7.3 helix A-Kv7.2 helix B (Q3A-Q2B) proximal CT/CaM complexes by solution methods at various Ca(2+)concentrations and determined them all to have a 1:1 stoichiometry. We then determined the crystal structure of the Q3A-Q2B/CaM complex at high Ca(2+) concentration to 2.0 Å resolution. CaM hugs the antiparallel coiled coil of helices A and B, braced together by an additional helix. The structure displays a hybrid apo-Ca(2+) CaM conformation even though four Ca(2+) ions are bound. Our results pinpoint unique interactions enabling the possible intersubunit pairing of Kv7.3 helix A and Kv7.2 helix B while underlining the potential importance of Kv7.3 helix A's role in stabilizing channel oligomerization. Also, the structure can be used to rationalize various channelopathic mutants. Functional testing of the chimeric channel found it to have a voltage-dependence similar to the M channel, thereby demonstrating helix A's importance in imparting gating properties.

PubMed: 27564677
DOI: 10.1021/acs.biochem.6b00477

実験手法

X-RAY DIFFRACTION (2 Å)