A structural determinant for the control of PIP_2 sensitivity in G protein-gated inward rectifier K^+ channels
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Abstract
This research was originally published in Journal of Biological Chemistry. Atsushi Inanobe, Atsushi Nakagawa, Takanori Matsuura and Yoshihisa Kurachi. A structural determinant for the control of PIP2 sensitivity in G protein-gated inward rectifier K^+ channels. Journal of Biological Chemistry. 2010; 285, 38517-38523. © the American Society for Biochemistry and Molecular Biology.
Inward 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 βγ subunits (Gβγ) 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 theNterminus and Asp-228 on the CD loop, which are known to be critically involved in Gβγ- 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.
Journal
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- Journal of Biological Chemistry
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Journal of Biological Chemistry 285 (49), 38517-38523, 2010-12
American Society for Biochemistry and Molecular Biology
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Details 詳細情報について
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- CRID
- 1050862643878825472
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- NII Article ID
- 120006770864
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- NII Book ID
- AA1202441X
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- ISSN
- 1083351X
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- HANDLE
- 11094/73656
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- Text Lang
- en
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- Article Type
- journal article
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- Data Source
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- IRDB
- CiNii Articles
- KAKEN