NMR analyses of the G{beta}{gamma} binding and conformational rearrangements of the c

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NMR analyses of the G{beta}{gamma} binding and conformational rearrangements of the cytoplasmic pore of G protein-activated inwardly rectifying potassium channel 1 (GIRK1).

Related Articles NMR analyses of the G{beta}{gamma} binding and conformational rearrangements of the cytoplasmic pore of G protein-activated inwardly rectifying potassium channel 1 (GIRK1).

J Biol Chem. 2010 Nov 12;

Authors: Yokogawa M, Osawa M, Takeuchi K, Mase Y, Shimada I

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 ?? subunits (G??) upon stimulation of G protein-coupled receptors, such as M2 acetylcholine receptor. The binding of G?? 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 G?? binding and the structural mechanism of the GIRK-gating have not been fully elucidated. Here, we have characterized the interaction between the CP region of GIRK and G??, by ITC and NMR. The ITC analyses indicated that four G?? molecules bind to a tetramer of the CP region of GIRK with a dissociation constant of 250 ?M. The NMR analyses revealed that the G?? 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.

PMID: 21075842 [PubMed - as supplied by publisher]



Source: PubMed