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学科主题药学
The Tetramerization Domain Potentiates Kv4 Channel Function by Suppressing Closed-State Inactivation
Tang, Yi-Quan1; Zhou, Jing-Heng1; Yang, Fan2; Zheng, Jie2; Wang, Kewei1,3
刊名BIOPHYSICAL JOURNAL
2014-09-02
DOI10.1016/j.bpj.2014.07.038
107期:5页:1090-1104
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Biophysics
研究领域[WOS]Biophysics
关键词[WOS]U-TYPE INACTIVATION ; INTRACELLULAR T1-T1 INTERFACE ; LONG-TERM POTENTIATION ; GATED K+ CHANNELS ; POTASSIUM CHANNELS ; 3-DIMENSIONAL STRUCTURE ; PYRAMIDAL NEURONS ; CALCIUM-CHANNELS ; LIVING CELLS ; T1 DOMAIN
英文摘要

A-type Kv4 potassium channels undergo a conformational change toward a nonconductive state at negative membrane potentials, a dynamic process known as pre-open closed states or closed-state inactivation (CSI). CSI causes inhibition of channel activity without the prerequisite of channel opening, thus providing a dynamic regulation of neuronal excitability, dendritic signal integration, and synaptic plasticity at resting. However, the structural determinants underlying Kv4 CSI remain largely unknown. We recently showed that the auxiliary KChIP4a subunit contains an N-terminal Kv4 inhibitory domain (KID) that directly interacts with Kv4.3 channels to enhance CSI. In this study, we utilized the KChIP4a KID to probe key structural elements underlying Kv4 CSI. Using fluorescence resonance energy transfer two-hybrid mapping and bimolecular fluorescence complementation-based screening combined with electrophysiology, we identified the intracellular tetrannerization (T1) domain that functions to suppress CSI and serves as a receptor for the binding of KID. Disrupting the Kv4.3 T1-T1 interaction interface by mutating C110A within the C3H1 Motif of T1 domain facilitated CSI and ablated the KID-mediated enhancement of CSI. Furthermore, replacing the Kv4.3 T1 domain with the T1 domain from Kv1.4 (without the C3H1 motif) or Kv2.1 (with the C3H1 motif) resulted in channels functioning with enhanced or suppressed CSI, respectively. Taken together, our findings reveal a novel (to our knowledge) role of the T1 domain in suppressing Kv4 CSI, and that KChIP4a KID directly interacts with the T1 domain to facilitate Kv4.3 CSI, thus leading to inhibition of channel function.

语种英语
WOS记录号WOS:000341275100010
项目编号31370741 ; 81221002 ; 2013CB531302 ; B07001
资助机构National Science Foundation of China ; Ministry of Science and Technology of China ; Ministry of Education of China (111 Project)
引用统计
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/61530
专题北京大学药学院
北京大学药学院_分子与细胞药理学系
作者单位1.Peking Univ, Sch Pharmaceut Sci, Dept Mol & Cellular Pharmacol, State Key Lab Nat & Biomimet Drugs, Beijing 100871, Peoples R China
2.Univ Calif Davis, Sch Med, Dept Physiol & Membrane Biol, Davis, CA 95616 USA
3.Peking Univ, PKU IDG McGovern Inst Brain Res, Beijing 100871, Peoples R China
推荐引用方式
GB/T 7714
Tang, Yi-Quan,Zhou, Jing-Heng,Yang, Fan,et al. The Tetramerization Domain Potentiates Kv4 Channel Function by Suppressing Closed-State Inactivation[J]. BIOPHYSICAL JOURNAL,2014,107(5):1090-1104.
APA Tang, Yi-Quan,Zhou, Jing-Heng,Yang, Fan,Zheng, Jie,&Wang, Kewei.(2014).The Tetramerization Domain Potentiates Kv4 Channel Function by Suppressing Closed-State Inactivation.BIOPHYSICAL JOURNAL,107(5),1090-1104.
MLA Tang, Yi-Quan,et al."The Tetramerization Domain Potentiates Kv4 Channel Function by Suppressing Closed-State Inactivation".BIOPHYSICAL JOURNAL 107.5(2014):1090-1104.
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