2K21

NMR structure of human KCNE1 in LMPG micelles at pH 6.0 and 40 degree C

2K21 の概要

• エントリーDOI: 10.2210/pdb2k21/pdb
• 分子名称: Potassium voltage-gated channel subfamily E member (1 entity in total)
• 機能のキーワード: kcne1, membrane protein, potassium channel, mink, auxilliary subunit, micelles, ion transport, ionic channel, potassium transport, transmembrane, transport, voltage-gated channel
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Membrane; Single-pass type I membrane protein (By similarity): Q6FHJ6
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 15706.87

構造登録者

Kang, C.,Tian, C.,Sonnichsen, F.D.,Smith, J.A.,Meiler, J.,George, A.L.,Vanoye, C.G.,Sanders, C.R.,Kim, H. (登録日: 2008-03-19, 公開日: 2008-12-09, 最終更新日: 2024-05-29)

主引用文献

Kang, C.,Tian, C.,Sonnichsen, F.D.,Smith, J.A.,Meiler, J.,George, A.L.,Vanoye, C.G.,Kim, H.J.,Sanders, C.R.
Structure of KCNE1 and implications for how it modulates the KCNQ1 potassium channel.
Biochemistry, 47:7999-8006, 2008

PubMed Abstract: KCNE1 is a single-span membrane protein that modulates the voltage-gated potassium channel KCNQ1 (K V7.1) by slowing activation and enhancing channel conductance to generate the slow delayed rectifier current ( I Ks) that is critical for the repolarization phase of the cardiac action potential. Perturbation of channel function by inherited mutations in KCNE1 or KCNQ1 results in increased susceptibility to cardiac arrhythmias and sudden death with or without accompanying deafness. Here, we present the three-dimensional structure of KCNE1. The transmembrane domain (TMD) of KCNE1 is a curved alpha-helix and is flanked by intra- and extracellular domains comprised of alpha-helices joined by flexible linkers. Experimentally restrained docking of the KCNE1 TMD to a closed state model of KCNQ1 suggests that KCNE1 slows channel activation by sitting on and restricting the movement of the S4-S5 linker that connects the voltage sensor to the pore domain. We postulate that this is an adhesive interaction that must be disrupted before the channel can be opened in response to membrane depolarization. Docking to open KCNQ1 indicates that the extracellular end of the KCNE1 TMD forms an interface with an intersubunit cleft in the channel that is associated with most known gain-of-function disease mutations. Binding of KCNE1 to this "gain-of-function cleft" may explain how it increases conductance and stabilizes the open state. These working models for the KCNE1-KCNQ1 complexes may be used to formulate testable hypotheses for the molecular bases of disease phenotypes associated with the dozens of known inherited mutations in KCNE1 and KCNQ1.

PubMed: 18611041
DOI: 10.1021/bi800875q

実験手法

SOLUTION NMR