View source for 3syc


==Crystal structure of the G protein-gated inward rectifier K+ channel GIRK2 (Kir3.2) D228N mutant==
<StructureSection load='3syc' size='340' side='right'caption='[[3syc]], [[Resolution|resolution]] 3.41&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3syc]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3SYC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3SYC 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]] 3.41&#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></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=3syc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3syc OCA], [https://pdbe.org/3syc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3syc RCSB], [https://www.ebi.ac.uk/pdbsum/3syc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3syc 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.
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== Publication Abstract from PubMed ==
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.

Crystal Structure of the Mammalian GIRK2 K(+) Channel and Gating Regulation by G Proteins, PIP(2), and Sodium.,Whorton MR, Mackinnon R Cell. 2011 Sep 30;147(1):199-208. PMID:21962516<ref>PMID:21962516</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 3syc" style="background-color:#fffaf0;"></div>

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