title: Modulation by clamping: Kv4 and KChIP interactions.
abstract: 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) alpha subunits to form a native complex that encodes major components of neuronal somatodendritic A-type K+ current, I(SA), in neurons and transient outward current, I(TO), 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. Here, I attempt to emphasize the interaction between KChIPs and Kv4 based on recent progress 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.
authors.affiliation: 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, 38 Xueyuan Road, Beijing 100083, China. wangkw@bjmu.edu.cn
authors.forename: Kewei
authors.initials: K
authors.lastname: Wang
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D006801:Humans; D051605:Kv Channel-Interacting Proteins / Q000502:physiology*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D021122:Protein Subunits / Q000502:physiology; D016415:Sequence Alignment; D051672:Shal Potassium Channels / Q000502:physiology*
chemical_list: D051605:Kv Channel-Interacting Proteins; D021122:Protein Subunits; D051672:Shal Potassium Channels