Coupling Gβγ-Dependent Activation to Channel Opening via Pore Elements in Inwardly Rectifying Potassium Channels

作者: Rona Sadja , Karine Smadja , Noga Alagem , Eitan Reuveny

DOI: 10.1016/S0896-6273(01)00242-2

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摘要: Abstract G protein–coupled inwardly rectifying potassium channels, GIRK/Kir3.x, are gated by the Gβγ subunits of protein. The molecular mechanism gating was investigated employing a novel yeast-based random mutagenesis approach that selected for channel mutants active in absence Gβγ. Mutations TM2 were found mimicked Gβγ-activated state. activity these independent receptor stimulation and availability heterologously expressed but depended on PtdIns(4,5)P 2 . results suggest region plays key role following binding phospholipid-dependent manner. This K + channels may be similar to involvement homologous prokaryotic KcsA and, thus, suggests evolutionary conservation structure.

参考文章(52)
DV Goeddel, E Chen, DW Leung, A method for random mutagenesis of a defined DNA segment using a modified polymerase chain reaction Technique. ,vol. 1, pp. 11- 15 ,(1989)
Eitan Reuveny, Paul A. Slesinger, James Inglese, Janine M. Morales, Jorge A. Iñiguez-Lluhi, Robert J. Lefkowitz, Henry R. Bourne, Yuh Nung Jan, Lily Y. Jan, Activation of the cloned muscarinic potassium channel by G protein βγ subunits Nature. ,vol. 370, pp. 143- 146 ,(1994) , 10.1038/370143A0
Diomedes E. Logothetis, Yoshihisa Kurachi, Jonas Galper, Eva J. Neer, David E. Clapham, The βγ subunits of GTP-binding proteins activate the muscarinic K + channel in heart Nature. ,vol. 325, pp. 321- 326 ,(1987) , 10.1038/325321A0
Kevin D. Wickman, Jorge A. Iñiguez-Lluhi, Philip A. Davenport, Ronald Taussig, Grigory B. Krapivinsky, Maurine E. Linder, Alfred G. Gilman, David E. Clapham, Recombinant G-protein βγ-subunits activate the muscarinic-gated atrial potassium channel Nature. ,vol. 368, pp. 255- 257 ,(1994) , 10.1038/368255A0
Hailin Zhang, Cheng He, Xixin Yan, Tooraj Mirshahi, Diomedes E. Logothetis, Activation of inwardly rectifying K+ channels by distinct PtdIns(4,5)P2 interactions. Nature Cell Biology. ,vol. 1, pp. 183- 188 ,(1999) , 10.1038/11103
Donato del Camino, Miguel Holmgren, Yi Liu, Gary Yellen, Blocker protection in the pore of a voltage-gated K+ channel and its structural implications. Nature. ,vol. 403, pp. 321- 325 ,(2000) , 10.1038/35002099
S-L Shyng, CG Nichols, Membrane Phospholipid Control of Nucleotide Sensitivity of KATP Channels Science. ,vol. 282, pp. 1138- 1141 ,(1998) , 10.1126/SCIENCE.282.5391.1138
Avijit Chakrabartty, John A. Schellman, Robert L. Baldwin, Large differences in the helix propensities of alanine and glycine Nature. ,vol. 351, pp. 586- 588 ,(1991) , 10.1038/351586A0
N F Lim, N Dascal, C Labarca, N Davidson, H A Lester, A G protein-gated K channel is activated via beta 2-adrenergic receptors and G beta gamma subunits in Xenopus oocytes. The Journal of General Physiology. ,vol. 105, pp. 421- 439 ,(1995) , 10.1085/JGP.105.3.421
Chou-Long Huang, Siyi Feng, Donald W. Hilgemann, Direct activation of inward rectifier potassium channels by PIP2 and its stabilization by Gβγ Nature. ,vol. 391, pp. 803- 806 ,(1998) , 10.1038/35882