3agw
From Proteopedia
Crystal Structure of the Cytoplasmic Domain of G-Protein-Gated Inward Rectifier Potassium Channel Kir3.2 in the absence of Na+
Structural highlights
DiseaseKCNJ6_MOUSE Defects in Kcnj6 are the cause of the weaver (wv) phenotype. Homozygous animals suffer from severe ataxia that is obvious by about the second postnatal week. The cerebellum of these animals is drastically reduced in size due to depletion of the major cell type of cerebellum, the granule cell neuron. Heterozygous animals are not ataxic but have an intermediate number of surviving granule cells. Male homozygotes are sterile, because of complete failure of sperm production. Both hetero- and homozygous animals undergo sporadic tonic-clonic seizures. FunctionKCNJ6_MOUSE This potassium channel is controlled by G proteins. It plays a role in granule cell differentiation, possibly via membrane hyperpolarization. Inward rectifier potassium channels are characterized by a greater tendency to allow potassium to flow into the cell rather than out of it. Their voltage dependence is regulated by the concentration of extracellular potassium; as external potassium is raised, the voltage range of the channel opening shifts to more positive voltages. The inward rectification is mainly due to the blockage of outward current by internal magnesium. 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 PubMedInward rectifier K(+) (Kir) channels are activated by phosphatidylinositol-(4,5)-bisphosphate (PIP(2)), but G protein-gated Kir (K(G)) channels further require either G protein betagamma subunits (Gbetagamma) or intracellular Na(+) for their activation. To reveal the mechanism(s) underlying this regulation, we compared the crystal structures of the cytoplasmic domain of K(G) channel subunit Kir3.2 obtained in the presence and the absence of Na(+). The Na(+)-free Kir3.2, but not the Na(+)-plus Kir3.2, possessed an ionic bond connecting the N terminus and the CD loop of the C terminus. Functional analyses revealed that the ionic bond between His-69 on the N terminus and Asp-228 on the CD loop, which are known to be critically involved in Gbetagamma- and Na(+)-dependent activation, lowered PIP(2) sensitivity. The conservation of these residues within the K(G) channel family indicates that the ionic bond is a character that maintains the channels in a closed state by controlling the PIP(2) sensitivity. A structural determinant for the control of PIP2 sensitivity in G protein-gated inward rectifier K+ channels.,Inanobe A, Nakagawa A, Matsuura T, Kurachi Y J Biol Chem. 2010 Dec 3;285(49):38517-23. Epub 2010 Sep 29. PMID:20880843[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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