Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Crystal structure of the mammalian GIRK2 K+ channel and gating regulation by G proteins, PIP2, and sodium.
Whorton MR, MacKinnon R.
???displayArticle.abstract???
G protein-gated K(+) channels (Kir3.1-Kir3.4) control electrical excitability in many different cells. Among their functions relevant to human physiology and disease, they regulate the heart rate and govern a wide range of neuronal activities. Here, we present the first crystal structures of a G protein-gated K(+) channel. By comparing the wild-type structure to that of a constitutively active mutant, we identify a global conformational change through which G proteins could open a G loop gate in the cytoplasmic domain. The structures of both channels in the absence and presence of PIP(2) suggest that G proteins open only the G loop gate in the absence of PIP(2), but in the presence of PIP(2) the G loop gate and a second inner helix gate become coupled, so that both gates open. We also identify a strategically located Na(+) ion-binding site, which would allow intracellular Na(+) to modulate GIRK channel activity. These data provide a structural basis for understanding multiligand regulation of GIRK channel gating.
Boudker,
Coupling substrate and ion binding to extracellular gate of a sodium-dependent aspartate transporter.
2007, Pubmed
Boudker,
Coupling substrate and ion binding to extracellular gate of a sodium-dependent aspartate transporter.
2007,
Pubmed Choi,
K+ channel mutations in adrenal aldosterone-producing adenomas and hereditary hypertension.
2011,
Pubmed Clarke,
Domain reorientation and rotation of an intracellular assembly regulate conduction in Kir potassium channels.
2010,
Pubmed Decher,
Impaired interaction between the slide helix and the C-terminus of Kir2.1: a novel mechanism of Andersen syndrome.
2007,
Pubmed
,
Xenbase Donaldson,
PIP2 binding residues of Kir2.1 are common targets of mutations causing Andersen syndrome.
2003,
Pubmed Doyle,
The structure of the potassium channel: molecular basis of K+ conduction and selectivity.
1998,
Pubmed Emsley,
Coot: model-building tools for molecular graphics.
2004,
Pubmed Finley,
betaL-betaM loop in the C-terminal domain of G protein-activated inwardly rectifying K(+) channels is important for G(betagamma) subunit activation.
2004,
Pubmed
,
Xenbase He,
Identification of a potassium channel site that interacts with G protein betagamma subunits to mediate agonist-induced signaling.
1999,
Pubmed He,
Identification of critical residues controlling G protein-gated inwardly rectifying K(+) channel activity through interactions with the beta gamma subunits of G proteins.
2002,
Pubmed Hibino,
Inwardly rectifying potassium channels: their structure, function, and physiological roles.
2010,
Pubmed Ho,
Molecular determinants for sodium-dependent activation of G protein-gated K+ channels.
1999,
Pubmed
,
Xenbase Ho,
HOLLOW: generating accurate representations of channel and interior surfaces in molecular structures.
2008,
Pubmed Ho,
Molecular mechanism for sodium-dependent activation of G protein-gated K+ channels.
1999,
Pubmed
,
Xenbase Huang,
Direct activation of inward rectifier potassium channels by PIP2 and its stabilization by Gbetagamma.
1998,
Pubmed
,
Xenbase Inanobe,
Structural diversity in the cytoplasmic region of G protein-gated inward rectifier K+ channels.
2007,
Pubmed Jiang,
The open pore conformation of potassium channels.
2002,
Pubmed Jiang,
X-ray structure of a voltage-dependent K+ channel.
2003,
Pubmed Jin,
Synthesis of a stable form of tertiapin: a high-affinity inhibitor for inward-rectifier K+ channels.
1999,
Pubmed
,
Xenbase Kofuji,
Evidence that neuronal G-protein-gated inwardly rectifying K+ channels are activated by G beta gamma subunits and function as heteromultimers.
1995,
Pubmed
,
Xenbase Kubo,
Primary structure and functional expression of a rat G-protein-coupled muscarinic potassium channel.
1993,
Pubmed
,
Xenbase Kuo,
Crystal structure of the potassium channel KirBac1.1 in the closed state.
2003,
Pubmed Lesage,
Molecular properties of neuronal G-protein-activated inwardly rectifying K+ channels.
1995,
Pubmed
,
Xenbase Lin,
A novel KCNJ11 mutation associated with congenital hyperinsulinism reduces the intrinsic open probability of beta-cell ATP-sensitive potassium channels.
2006,
Pubmed Logothetis,
The beta gamma subunits of GTP-binding proteins activate the muscarinic K+ channel in heart.
,
Pubmed Long,
Crystal structure of a mammalian voltage-dependent Shaker family K+ channel.
2005,
Pubmed Long,
Atomic structure of a voltage-dependent K+ channel in a lipid membrane-like environment.
2007,
Pubmed Lopatin,
Potassium channel block by cytoplasmic polyamines as the mechanism of intrinsic rectification.
1994,
Pubmed
,
Xenbase Lüscher,
Emerging roles for G protein-gated inwardly rectifying potassium (GIRK) channels in health and disease.
2010,
Pubmed Ma,
Role of ER export signals in controlling surface potassium channel numbers.
2001,
Pubmed
,
Xenbase Matsuda,
Ohmic conductance through the inwardly rectifying K channel and blocking by internal Mg2+.
,
Pubmed Murshudov,
Refinement of macromolecular structures by the maximum-likelihood method.
1997,
Pubmed Nishida,
Crystal structure of a Kir3.1-prokaryotic Kir channel chimera.
2007,
Pubmed Nishida,
Structural basis of inward rectification: cytoplasmic pore of the G protein-gated inward rectifier GIRK1 at 1.8 A resolution.
2002,
Pubmed Pegan,
Cytoplasmic domain structures of Kir2.1 and Kir3.1 show sites for modulating gating and rectification.
2005,
Pubmed
,
Xenbase Pfaffinger,
GTP-binding proteins couple cardiac muscarinic receptors to a K channel.
,
Pubmed Plaster,
Mutations in Kir2.1 cause the developmental and episodic electrical phenotypes of Andersen's syndrome.
2001,
Pubmed
,
Xenbase Reuveny,
Activation of the cloned muscarinic potassium channel by G protein beta gamma subunits.
1994,
Pubmed
,
Xenbase Spassova,
Coupled ion movement underlies rectification in an inward-rectifier K+ channel.
1998,
Pubmed
,
Xenbase Sui,
Activation of the atrial KACh channel by the betagamma subunits of G proteins or intracellular Na+ ions depends on the presence of phosphatidylinositol phosphates.
1998,
Pubmed
,
Xenbase Sui,
Na+ activation of the muscarinic K+ channel by a G-protein-independent mechanism.
1996,
Pubmed
,
Xenbase Tao,
Crystal structure of the eukaryotic strong inward-rectifier K+ channel Kir2.2 at 3.1 A resolution.
2009,
Pubmed
,
Xenbase Vagin,
An approach to multi-copy search in molecular replacement.
2000,
Pubmed Wickman,
Recombinant G-protein beta gamma-subunits activate the muscarinic-gated atrial potassium channel.
1994,
Pubmed Yang,
Control of rectification and permeation by residues in two distinct domains in an inward rectifier K+ channel.
1995,
Pubmed
,
Xenbase Yokogawa,
NMR analyses of the Gbetagamma binding and conformational rearrangements of the cytoplasmic pore of G protein-activated inwardly rectifying potassium channel 1 (GIRK1).
2011,
Pubmed Zhang,
Activation of inwardly rectifying K+ channels by distinct PtdIns(4,5)P2 interactions.
1999,
Pubmed
,
Xenbase
