View source for 4kfm


==Crystal structure of the G protein-gated inward rectifier K+ channel GIRK2 (Kir3.2) in complex with the beta-gamma G protein subunits==
<StructureSection load='4kfm' size='340' side='right'caption='[[4kfm]], [[Resolution|resolution]] 3.45&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4kfm]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4KFM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4KFM FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.45&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=LMT:DODECYL-BETA-D-MALTOSIDE'>LMT</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=PIO:[(2R)-2-OCTANOYLOXY-3-[OXIDANYL-[(1R,2R,3S,4R,5R,6S)-2,3,6-TRIS(OXIDANYL)-4,5-DIPHOSPHONOOXY-CYCLOHEXYL]OXY-PHOSPHORYL]OXY-PROPYL]+OCTANOATE'>PIO</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4kfm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4kfm OCA], [https://pdbe.org/4kfm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4kfm RCSB], [https://www.ebi.ac.uk/pdbsum/4kfm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4kfm ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/KCNJ6_MOUSE KCNJ6_MOUSE] Defects in Kcnj6 are the cause of the weaver (wv) phenotype. Homozygous animals suffer from severe ataxia that is obvious by about the second postnatal week. The cerebellum of these animals is drastically reduced in size due to depletion of the major cell type of cerebellum, the granule cell neuron. Heterozygous animals are not ataxic but have an intermediate number of surviving granule cells. Male homozygotes are sterile, because of complete failure of sperm production. Both hetero- and homozygous animals undergo sporadic tonic-clonic seizures.
== Function ==
[https://www.uniprot.org/uniprot/KCNJ6_MOUSE KCNJ6_MOUSE] This potassium channel is controlled by G proteins. It plays a role in granule cell differentiation, possibly via membrane hyperpolarization. Inward rectifier potassium channels are characterized by a greater tendency to allow potassium to flow into the cell rather than out of it. Their voltage dependence is regulated by the concentration of extracellular potassium; as external potassium is raised, the voltage range of the channel opening shifts to more positive voltages. The inward rectification is mainly due to the blockage of outward current by internal magnesium.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
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 A resolution crystal structure of the mammalian GIRK2 channel in complex with betagamma 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 betagamma 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.

X-ray structure of the mammalian GIRK2-betagamma G-protein complex.,Whorton MR, MacKinnon R Nature. 2013 Jun 13;498(7453):190-7. doi: 10.1038/nature12241. Epub 2013 Jun 5. PMID:23739333<ref>PMID:23739333</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4kfm" style="background-color:#fffaf0;"></div>

==See Also==
*[[Potassium channel 3D structures|Potassium channel 3D structures]]
*[[Transducin 3D structures|Transducin 3D structures]]
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: MacKinnon R]]
[[Category: Whorton MR]]