NMR analyses of the Gβγ binding and conformational rearrangements of the cytoplasmic pore of G protein-activated inwardly rectifying potassium channel 1 (GIRK1)

Mariko Yokogawa, Masanori Osawa, Koh Takeuchi, Yoko Mase, Ichio Shimada

研究成果: Article査読

39 被引用数 (Scopus)

抄録

G protein-activated inwardly rectifying potassium channel (GIRK) plays crucial roles in regulating heart rate and neuronal excitability in eukaryotic cells. GIRK is activated by the direct binding of heterotrimeric G protein βγ subunits (Gβγ) upon stimulation of G protein-coupled receptors, such as M2 acetylcholine receptor. The binding of Gβγ to the cytoplasmic pore (CP) region of GIRK causes structural rearrangements, which are assumed to open the transmembrane ion gate. However, the crucial residues involved in the Gβγ binding and the structural mechanism of GIRK gating have not been fully elucidated. Here, we have characterized the interaction between the CP region of GIRK and Gβγ, by ITC and NMR. The ITC analyses indicated that four Gβγ molecules bind to a tetramer of the CP region of GIRK with a dissociation constant of 250 μM. The NMR analyses revealed that the Gβγ binding site spans two neighboring subunits of the GIRK tetramer, which causes conformational rearrangements between subunits. A possible binding mode and mechanism of GIRK gating are proposed.

本文言語English
ページ(範囲)2215-2223
ページ数9
ジャーナルJournal of Biological Chemistry
286
3
DOI
出版ステータスPublished - 2011 1 21
外部発表はい

ASJC Scopus subject areas

  • 生化学
  • 分子生物学
  • 細胞生物学

フィンガープリント

「NMR analyses of the Gβγ binding and conformational rearrangements of the cytoplasmic pore of G protein-activated inwardly rectifying potassium channel 1 (GIRK1)」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

引用スタイル