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学科主题: 药学
题名:
The Tetramerization Domain Potentiates Kv4 Channel Function by Suppressing Closed-State Inactivation
作者: Tang, Yi-Quan1; Zhou, Jing-Heng1; Yang, Fan2; Zheng, Jie2; Wang, Kewei1,3
刊名: BIOPHYSICAL JOURNAL
发表日期: 2014-09-02
DOI: 10.1016/j.bpj.2014.07.038
卷: 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
所属项目编号: 31370741 ; 81221002 ; 2013CB531302 ; B07001
项目资助者: National Science Foundation of China ; Ministry of Science and Technology of China ; Ministry of Education of China (111 Project)
WOS记录号: WOS:000341275100010
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内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/61530
Appears in Collections:北京大学药学院_期刊论文

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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

Recommended Citation:
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.
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