科研之友
微信
新浪微博
Facebook
分享链接
摘要
Inward rectifier K+ (Kir) channels are activated by phosphatidylinositol-(4,5)-bisphosphate (PIP2), but G protein-gated Kir (K-G) channels further require either G protein beta gamma subunits (G beta gamma) 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 G beta gamma- and Na+-dependent activation, lowered PIP2 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 PIP2 sensitivity.
- 出版日期2010-12-3
