“G-蛋白耦合受體”(GPCRs)的激發(fā)導(dǎo)致G-蛋白亞單元GG 和 G 從GPCR的細(xì)胞內(nèi)表面上釋放。GGG然后可以結(jié)合到“由GGG蛋白門控的內(nèi)向整理器K+”(GIRK) 通道上,，并激發(fā)后者,，使該通道的孔打開。GIRK通道的打開驅(qū)動膜電壓朝向“靜息電位”（“能斯特電位”）變化,，這將使膜去極化的速度降低,。
在這篇文章中，Matthew Whorton 和 Roderick MacKinnon解決了一個哺乳動物GIRK2通道在通過 G-蛋白亞單元存在時的X-射線晶體結(jié)構(gòu),。雖然射射 G-蛋白亞單元的總體結(jié)構(gòu)實(shí)質(zhì)上與在GG 或 GIRK存在時是一樣的,，但GIRK 和 GIRK–G 的結(jié)構(gòu)卻很不相同。
該結(jié)構(gòu)還顯示了起信號作用的脂質(zhì)PIP2和細(xì)胞內(nèi)Na+離子是怎樣幫助調(diào)控GIRKs的活性的,。(生物谷Bioon.com)
生物谷推薦英文摘要：
Nature doi:10.1038/nature12241
X-ray structure of the mammalian GIRK2–βγ G-protein complex
Matthew R. Whorton & Roderick MacKinnon
G-protein-gated inward rectifier K+ (GIRK) channels allow neurotransmitters, through G-protein-coupled receptor stimulation, to control cellular electrical excitability. In cardiac and neuronal cells this control regulates heart rate and neural circuit activity, respectively. Here we present the 3.5?? resolution crystal structure of the mammalian GIRK2 channel in complex with βγ G-protein subunits, the central signalling complex that links G-protein-coupled receptor stimulation to K+ channel activity. Short-range atomic and long-range electrostatic interactions stabilize four βγ G-protein subunits at the interfaces between four K+ channel subunits, inducing a pre-open state of the channel. The pre-open state exhibits a conformation that is intermediate between the closed conformation and the open conformation of the constitutively active mutant. The resultant structural picture is compatible with ‘membrane delimited’ activation of GIRK channels by G proteins and the characteristic burst kinetics of channel gating. The structures also permit a conceptual understanding of how the signalling lipid phosphatidylinositol-4,5-bisphosphate (PIP2) and intracellular Na+ ions participate in multi-ligand regulation of GIRK channels.
