Structural basis of inward rectification: cytoplasmic pore of the G protein-gated inward rectifier GIRK1 at 1.8 A resolution.
Inward rectifier K(+) channels govern the resting membrane voltage in many cells. Regulation of these ion channels via G protein-coupled receptor signaling underlies the control of heart rate and the actions of neurotransmitters in the central nervous system. We have determined the protein structure formed by the intracellular N- and C termini of the G protein-gated inward rectifier K(+) channel GIRK1 at 1.8 A resolution. A cytoplasmic pore, conserved among inward rectifier K(+) channels, extends the ion pathway to 60 A, nearly twice the length of a canonical transmembrane K(+) channel. The cytoplasmic pore is lined by acidic and hydrophobic amino acids, creating a favorable environment for polyamines, which block the pore. These results explain in structural and chemical terms the basis of inward rectification, and they also have implications for G protein regulation of GIRK channels.
Nishida
Motohiko
M
Howard Hughes Medical Institute and Laboratory of Molecular Neurobiology and Biophysics, Rockefeller University, New York, NY 10021, USA.
MacKinnon
Roderick
R
D000595:Amino Acid Sequence / Q000502:physiology; D000596:Amino Acids / Q000737:chemistry; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism* / Q000648:ultrastructure; D003593:Cytoplasm / Q000378:metabolism* / Q000648:ultrastructure; D005057:Eukaryotic Cells / Q000378:metabolism* / Q000648:ultrastructure; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D019204:GTP-Binding Proteins / Q000378:metabolism*; D008564:Membrane Potentials / Q000502:physiology; D051379:Mice; D011073:Polyamines / Q000494:pharmacology; D015221:Potassium Channels / Q000378:metabolism* / Q000648:ultrastructure; D024661:Potassium Channels, Inwardly Rectifying; D017434:Protein Structure, Tertiary / Q000502:physiology
D000596:Amino Acids; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; C497067:Kcnj3 protein, mouse; D011073:Polyamines; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D019204:GTP-Binding Proteins