X-ray structure of the mammalian GIRK2-beta gamma G-protein complex

Article

关键词: BETA-GAMMA-SUBUNITS;    SODIUM-DEPENDENT ACTIVATION;    RECTIFYING K+ CHANNELS;    CRYSTAL-STRUCTURE;    POTASSIUM CHANNELS;    RECEPTORS;    BINDING;    SYSTEM;    PIP2;    RGS9;   

DOI  :  10.1038/nature12241

来源: SCIE

【 摘 要 】

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 angstrom resolution crystal structure of the mammalian GIRK2 channel in complex with beta gamma 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 beta gamma 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.

【 授权许可】

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