2ovc
Crystal structure of a coiled-coil tetramerization domain from Kv7.4 channels
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OverviewOverview
Kv7.x (KCNQ) voltage-gated potassium channels form the cardiac and auditory I(Ks) current and the neuronal M-current. The five Kv7 subtypes have distinct assembly preferences encoded by a C-terminal cytoplasmic assembly domain, the A-domain Tail. Here, we present the high-resolution structure of the Kv7.4 A-domain Tail together with biochemical experiments that show that the domain is a self-assembling, parallel, four-stranded coiled coil. Structural analysis and biochemical studies indicate conservation of the coiled coil in all Kv7 subtypes and that a limited set of interactions encode assembly specificity determinants. Kv7 mutations have prominent roles in arrhythmias, deafness, and epilepsy. The structure together with biochemical data indicate that A-domain Tail arrhythmia mutations cluster on the solvent-accessible surface of the subunit interface at a likely site of action for modulatory proteins. Together, the data provide a framework for understanding Kv7 assembly specificity and the molecular basis of a distinct set of Kv7 channelopathies.
DiseaseDisease
Known disease associated with this structure: Deafness, autosomal dominant 2 OMIM:[603537]
About this StructureAbout this Structure
2OVC is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
Structural insight into KCNQ (Kv7) channel assembly and channelopathy., Howard RJ, Clark KA, Holton JM, Minor DL Jr, Neuron. 2007 Mar 1;53(5):663-75. PMID:17329207
Page seeded by OCA on Thu Feb 21 18:22:57 2008