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PDBsum entry 4kfm
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Metal transport
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PDB id
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4kfm
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Contents |
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328 a.a.
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339 a.a.
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60 a.a.
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References listed in PDB file
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Key reference
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Title
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X-Ray structure of the mammalian girk2-βγ G-Protein complex.
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Authors
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M.R.Whorton,
R.Mackinnon.
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Ref.
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Nature, 2013,
498,
190-197.
[DOI no: ]
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PubMed id
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Abstract
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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.
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