2nz0
From Proteopedia
Crystal structure of potassium channel Kv4.3 in complex with its regulatory subunit KChIP1 (CASP Target)
Structural highlights
Disease[KCND3_HUMAN] Note=KCND3 rare variants may confer risk for lethal ventricular arrhytmias and be associated with autopsy-negative sudden unexplained death syndrome (SUDS).[1] Function[KCIP1_HUMAN] Regulatory subunit of Kv4/D (Shal)-type voltage-gated rapidly inactivating A-type potassium channels. Probably modulates channels density, inactivation kinetics and rate of recovery from inactivation in a calcium-dependent and isoform-specific manner. In vitro, modulates KCND1/Kv4.1 and KCND2/Kv4.2 currents. Seems to be involved in KCND2 trafficking to the cell surface.[2] [3] [4] [KCND3_HUMAN] Pore-forming (alpha) subunit of voltage-gated rapidly inactivating A-type potassium channels. May contribute to I(To) current in heart and I(Sa) current in neurons. Channel properties are modulated by interactions with other alpha subunits and with regulatory subunits.[5] [6] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedKChIPs coassemble with pore-forming Kv4 alpha subunits to form a native complex in the brain and heart and regulate the expression and gating properties of Kv4 K(+) channels, but the mechanisms underlying these processes are unknown. Here we report a co-crystal structure of the complex of human Kv4.3 N-terminus and KChIP1 at a 3.2-A resolution. The structure reveals a unique clamping action of the complex, in which a single KChIP1 molecule, as a monomer, laterally clamps two neighboring Kv4.3 N-termini in a 4:4 manner, forming an octamer. The proximal N-terminal peptide of Kv4.3 is sequestered by its binding to an elongated groove on the surface of KChIP1, which is indispensable for the modulation of Kv4.3 by KChIP1, and the same KChIP1 molecule binds to an adjacent T1 domain to stabilize the tetrameric Kv4.3 channels. Taken together with biochemical and functional data, our findings provide a structural basis for the modulation of Kv4 by KChIPs. Structural basis for modulation of Kv4 K+ channels by auxiliary KChIP subunits.,Wang H, Yan Y, Liu Q, Huang Y, Shen Y, Chen L, Chen Y, Yang Q, Hao Q, Wang K, Chai J Nat Neurosci. 2007 Jan;10(1):32-9. Epub 2006 Dec 24. PMID:17187064[7] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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Categories: Human | Large Structures | Chen, L | Shen, Y | Wang, H | Wang, K | Yan, Y | Kchip1 | Kv4 3 | Membrane protein
