A structural determinant for the control of PIP2 sensitivity in G protein-gated inward rectifier K+ channels


Atsushi Inanobe‡§, Atsushi Nakagawa, Takanori Matsuura, and Yoshitaka Kurachi‡§

Department of Pharmacology, Graduate School of Medicine
§§Center for Advanced Medical Engineering and Informatics
Laboratory of Supramolecular Crystallography
Laboratory of Protein Informatics, Institute for Protein Research, Osaka University, Osaka 565-0871, Japan

Journal of Biological Chemistry 285(49), 38517-38523 (2010)

Inward rectifier K+ (Kir) channels are activated by phosphatidylinositol-(4,5)-bisphosphate (PIP2), but G protein-gated Kir (KG) 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 KG 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 Gβγ- and Na+-dependent activation, lowered PIP2 sensitivity. The conservation of these residues within the KG channel family indicates that the ionic bond is a character that maintains the channels in a closed state by controlling the PIP2 sensitivity.




Back toResearch Activity


MATSUURA Takanori
t.matsuu%gmail.com (Please change the mark “%” to “@”)

Valid XHTML 1.1! Valid CSS!