Crystal structure and functional analysis of the HERG potassium channel N terminus: A eukaryotic PAS domain

被引:374
作者
Cabral, JHM
Lee, A
Cohen, SL
Chait, BT
Li, M
Mackinnon, R
机构
[1] Rockefeller Univ, Lab Mol Neurobiol & Biophys, New York, NY 10021 USA
[2] Rockefeller Univ, Lab Mass Spectrometry & Gaseous Ion Chem, New York, NY 10021 USA
[3] Rockefeller Univ, Howard Hughes Med Inst, New York, NY 10021 USA
[4] Johns Hopkins Univ, Sch Med, Dept Physiol, Baltimore, MD 21205 USA
关键词
D O I
10.1016/S0092-8674(00)81635-9
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The HERG voltage-dependent K+ channel plays a role in cardiac electrical excitability, and when defective, it underlies one form of the long QT syndrome. We have determined the crystal structure of the HERG K+ channel N-terminal domain and studied its role as a modifier of gating using electrophysiological methods. The domain is similar in structure to a bacterial light sensor photoactive yellow protein and provides the first three-dimensional model of a eukaryotic PAS domain. Scanning mutagenesis of the domain surface has allowed the identification of a hydrophobic "hot spot" forming a putative interface with the body of the K+ channel to which it tightly binds. The presence, of the domain attached to the channel slows the rate of deactivation. Given the roles of PAS domains in biology, we propose that the HERG N-terminal domain has a regulatory function.
引用
收藏
页码:649 / 655
页数:7
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