Insights into hERG K+ channel structure and function from NMR studies

被引：10
作者：
Ng, Chai Ann [1 ,2 ,3 ]
Torres, Allan M. [4 ]
Pages, Guilhem [5 ]
Kuchel, Philip W. [2 ,5 ]
Vandenberg, Jamie I. [1 ,2 ,3 ]
机构：
[1] Victor Chang Cardiac Res Inst, Mol Cardiol & Biophys Div, Mark Cowley Lidwill Res Programme Cardiac Electro, Darlinghurst, NSW 2010, Australia
[2] Univ Sydney, Sch Mol Biosci, Sydney, NSW 2006, Australia
[3] Univ New S Wales, St Vincents Clin Sch, Darlinghurst, NSW 2052, Australia
[4] Univ Western Sydney, Sch Biomed & Hlth Sci, Penrith, NSW 2751, Australia
[5] Inst Biomed Sci, Singapore Bioimaging Consortium, Mech Syst Biol NMR Grp, Singapore 138667, Singapore
来源：
EUROPEAN BIOPHYSICS JOURNAL WITH BIOPHYSICS LETTERS | 2013年 / 42卷 / 01期
基金：
澳大利亚研究理事会; 英国医学研究理事会;
关键词：
NMR; hERG; PAS domain; S4-S5; linker; Pore domain; CNBHD; LONG QT SYNDROME; GENE POTASSIUM CHANNELS; HUMAN INWARD RECTIFIER; AMINO-TERMINAL DOMAIN; CARDIAC-ARRHYTHMIA; MOLECULAR-BASIS; PREPARATIVE-SCALE; MEMBRANE-PROTEINS; CRYSTAL-STRUCTURE; LIPID-MEMBRANE;
D O I：
10.1007/s00249-012-0808-6
中图分类号：
Q6 [生物物理学];
学科分类号：
071011 ;
摘要：
The unique gating kinetics of hERG K+ channels are critical for normal cardiac repolarization, and patients with mutations in hERG have a markedly increased risk of cardiac arrhythmias and sudden cardiac arrest. HERG K+ channels are also remarkably promiscuous with respect to drug binding, which has been a very significant problem for the pharmaceutical industry. Here, we review the progress that has been made in understanding the structure and function of hERG K+ channels with a particular focus on nuclear magnetic resonance studies of the domains of the hERG K+ channel.
引用
收藏
页码：71 / 79
页数：9
相关论文
共 46 条
[1]   Identification of the cyclic-nucleotide-binding domain as a conserved determinant of ion-channel cell-surface localization [J].
Akhavan, A ;
Atanasiu, R ;
Noguchi, T ;
Han, W ;
Holder, N ;
Shrier, A .
JOURNAL OF CELL SCIENCE, 2005, 118 (13) :2803-2812
[2]   Identification of a COOH-terminal segment involved in maturation and stability of human ether-a-go-go-related gene potassium channels [J].
Akhavan, A ;
Atanasiu, R ;
Shrier, A .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (41) :40105-40112
[3]  
Apponyi Margit A., 2008, V426, P257, DOI 10.1007/978-1-60327-058-8_16
[4]   Functional characterization of the C-terminus of the human ether-a-go-go-related gene K+ channel (HERG) [J].
Aydar, E ;
Palmer, C .
JOURNAL OF PHYSIOLOGY-LONDON, 2001, 534 (01) :1-14
[5]   Structure of the carboxy-terminal region of a KCNH channel [J].
Brelidze, Tinatin I. ;
Carlson, Anne E. ;
Sankaran, Banumathi ;
Zagotta, William N. .
NATURE, 2012, 481 (7382) :530-U147
[6]   Absence of Direct Cyclic Nucleotide Modulation of mEAG1 and hERG1 Channels Revealed with Fluorescence and Electrophysiological Methods [J].
Brelidze, Tinatin I. ;
Carlson, Anne E. ;
Zagotta, William N. .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2009, 284 (41) :27989-27997
[7]   Crystal structure and functional analysis of the HERG potassium channel N terminus: A eukaryotic PAS domain [J].
Cabral, JHM ;
Lee, A ;
Cohen, SL ;
Chait, BT ;
Li, M ;
Mackinnon, R .
CELL, 1998, 95 (05) :649-655
[8]   The S4-S5 Linker Acts as a Signal Integrator for hERG K+ Channel Activation and Deactivation Gating [J].
Chai Ann Ng ;
Perry, Matthew D. ;
Tan, Peter S. ;
Hill, Adam P. ;
Kuchel, Philip W. ;
Vandenberg, Jamie I. .
PLOS ONE, 2012, 7 (02)
[9]   A MOLECULAR-BASIS FOR CARDIAC-ARRHYTHMIA - HERG MUTATIONS CAUSE LONG QT SYNDROME [J].
CURRAN, ME ;
SPLAWSKI, I ;
TIMOTHY, KW ;
VINCENT, GM ;
GREEN, ED ;
KEATING, MT .
CELL, 1995, 80 (05) :795-803
[10]   The structure of the potassium channel:: Molecular basis of K+ conduction and selectivity [J].
Doyle, DA ;
Cabral, JM ;
Pfuetzner, RA ;
Kuo, AL ;
Gulbis, JM ;
Cohen, SL ;
Chait, BT ;
MacKinnon, R .
SCIENCE, 1998, 280 (5360) :69-77
12345