Modulation by Clamping: Kv4 and KChIP Interactions
(0) Functional modulation of Kv4 channels by auxiliary KChIPs is of an extreme complexit-y. Recentco-crystal structure of Kv4 N-terminus/KChIP complex reveals a unique clam-ping mode of Kv4 andKChIP interaction with two-contact interfaces being involved inthe complex interaction.Theclamping mode has provided a structural framework in unde-rstanding the effects of KChIP1 on Kv4channel gating and possible surface expressio-n. Yet，many interesting questions still remain to beanswered. Does the second inte-rface affect the channel trafficking in any way besides promoting thetetrameric ass-embly? Since all KChIPs share the core regions but vary in their N-termini，do othe-r KChIPs form the structure similar to KChIP1? Can the clamping structure of KChIP1account forthe functional differences among other KChIPs（KChIP4a for instance) on K-v4 function?Understanding the molecular mechanism of Kv4 and KChIP interaction may lead to a betterunderstanding of the channel biology and function of native A-type K-v4 K+ currents. Because of therelevance of these findings to neuronal excitability,small molecules aimed at specific modulation ofKv4 and KChIP interaction may have th-erapeutic potentials for treatment of membraneexcitability-related disease conditio-ns.
神经元 分子机制 钾离子电流
KeWei Wang
Neuroscience Research Institute and Department of Neurobiology,Key Laboratory for Neuroscience of the Ministry of Education,Center for Protein Sciences, Peking University Health Science Center
国内会议
长沙
英文
329-337
2008-07-25（万方平台首次上网日期，不代表论文的发表时间）