电压门控钾离子通道是神经元或心肌细胞动作电位复极过程中重要的蛋白分子。本项目的研究目的旨在通过结构生物学手段解析Kv4-N/KChIPs复合体晶体的原子结构，并结合生化、分子生物学和电生理记录等方法，阐明Kv4与KChIP（K+ channel interacting protein）相互作用的结构基础和分子调节机制。探讨离子通道?亚基和辅助亚基相互作用的结构和分子机制不仅对于理解神经和心脏动作电位的调节机理有着重要的理论意义，亦对基于靶标结构而设计创新和特异的化学小分子调节神经元兴奋性有着实际的指导作用。通过4年来的研究，圆满完成本项目的实验计划。随着研究的深入，还进一步得到有趣的原创性结果，为深入提供了线索。

The rapidly inactivating (A-type) potassium channels regulate membrane excitability that defines the fundamental mechanism of neuronal functions such as pain signaling. Cytosolic Kv channel-interacting proteins KChIPs that belong to neuronal calcium sensor (NCS) family of calcium binding EF-hand proteins co-assemble with Kv4 (Shal) α subunits to form a native complex that encodes major components of neuronal somatodendritic A-type K+ current, ISA, in neurons and transient outward current, ITO, in cardiac myocytes. The specific binding of auxiliary KChIPs to the Kv4 N-terminus results in modulation of gating properties, surface expression and subunit assembly of Kv4 channels. Through the support of this grant we have stidued the interaction between KChIPs and Kv4 channels. A great progress has been made in understanding the structure complex in which a single KChIP1 molecule laterally clamps two neighboring Kv4.3 N-termini in a 4:4 manner. Greater insights into molecular mechanism between KChIPs and Kv4 interaction may provide therapeutic potentials of designing compounds aimed at disrupting the protein-protein interaction for treatment of membrane excitability-related disorders.

电压门控钾离子通道是神经元或心肌细胞动作电位复极过程中重要的蛋白分子。本项目的研究目的旨在通过结构生物学手段解析Kv4-N/KChIPs复合体晶体的原子结构，并结合生化、分子生物学和电生理记录等方法，阐明Kv4与KChIP（K+ channel interacting protein）相互作用的结构基础和分子调节机制。探讨离子通道?亚基和辅助亚基相互作用的结构和分子机制不仅对于理解神经和心脏动作电位的调节机理有着重要的理论意义，亦对基于靶标结构而设计创新和特异的化学小分子调节神经元兴奋性有着实际的指导作用。通过4年来的研究，圆满完成本项目的实验计划。随着研究的深入，还进一步得到有趣的原创性结果，为深入提供了线索。