4KFM

Crystal structure of the G protein-gated inward rectifier K+ channel GIRK2 (Kir3.2) in complex with the beta-gamma G protein subunits

Summary for 4KFM

• Entry DOI: 10.2210/pdb4kfm/pdb
• Related: 3SYA 3SYC 3SYO 3SYP 3SYQ
• Descriptor: G protein-activated inward rectifier potassium channel 2, Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1, Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2, ... (7 entities in total)
• Functional Keywords: metal transport, ion channel, potassium channel, inward rectification, sodium binding, pip2 binding, g protein binding
• Biological source: Mus musculus (mouse); More
• Cellular location: Membrane; Multi-pass membrane protein (By similarity): Q8C4T8; Cell membrane; Lipid-anchor; Cytoplasmic side (Potential): P59768
• Total number of polymer chains: 3
• Total formula weight: 85672.47

Authors

Whorton, M.R.,MacKinnon, R. (deposition date: 2013-04-27, release date: 2013-06-12, Last modification date: 2024-11-06)

Primary citation

Whorton, M.R.,MacKinnon, R.
X-ray structure of the mammalian GIRK2-beta gamma G-protein complex.
Nature, 498:190-197, 2013

PubMed Abstract: 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 Å 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.

PubMed: 23739333
DOI: 10.1038/nature12241

Experimental method

X-RAY DIFFRACTION (3.45 Å)