7wf4: Difference between revisions
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==== | ==Composite map of human Kv1.3 channel in dalazatide-bound state with beta subunits== | ||
<StructureSection load='7wf4' size='340' side='right'caption='[[7wf4]]' scene=''> | <StructureSection load='7wf4' size='340' side='right'caption='[[7wf4]], [[Resolution|resolution]] 3.40Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br> | <table><tr><td colspan='2'>[[7wf4]] is a 12 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7WF4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7WF4 FirstGlance]. <br> | ||
</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=7wf4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7wf4 OCA], [https://pdbe.org/7wf4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7wf4 RCSB], [https://www.ebi.ac.uk/pdbsum/7wf4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7wf4 ProSAT]</span></td></tr> | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.4Å</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=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</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=7wf4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7wf4 OCA], [https://pdbe.org/7wf4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7wf4 RCSB], [https://www.ebi.ac.uk/pdbsum/7wf4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7wf4 ProSAT]</span></td></tr> | |||
</table> | </table> | ||
== Function == | |||
[https://www.uniprot.org/uniprot/KCNA3_HUMAN KCNA3_HUMAN] Mediates the voltage-dependent potassium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a potassium-selective channel through which potassium ions may pass in accordance with their electrochemical gradient. | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
We report two structures of the human voltage-gated potassium channel (Kv) Kv1.3 in immune cells alone (apo-Kv1.3) and bound to an immunomodulatory drug called dalazatide (dalazatide-Kv1.3). Both the apo-Kv1.3 and dalazatide-Kv1.3 structures are in an activated state based on their depolarized voltage sensor and open inner gate. In apo-Kv1.3, the aromatic residue in the signature sequence (Y447) adopts a position that diverges 11 A from other K(+) channels. The outer pore is significantly rearranged, causing widening of the selectivity filter and perturbation of ion binding within the filter. This conformation is stabilized by a network of intrasubunit hydrogen bonds. In dalazatide-Kv1.3, binding of dalazatide to the channel's outer vestibule narrows the selectivity filter, Y447 occupies a position seen in other K(+) channels, and this conformation is stabilized by a network of intersubunit hydrogen bonds. These remarkable rearrangements in the selectivity filter underlie Kv1.3's transition into the drug-blocked state. | |||
Rearrangement of a unique Kv1.3 selectivity filter conformation upon binding of a drug.,Tyagi A, Ahmed T, Jian S, Bajaj S, Ong ST, Goay SSM, Zhao Y, Vorobyov I, Tian C, Chandy KG, Bhushan S Proc Natl Acad Sci U S A. 2022 Feb 1;119(5):e2113536119. doi: , 10.1073/pnas.2113536119. PMID:35091471<ref>PMID:35091471</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 7wf4" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Potassium channel 3D structures|Potassium channel 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: | [[Category: Ahmed T]] | ||
[[Category: Bajaj S]] | |||
[[Category: Bhushan S]] | |||
[[Category: Chandy KG]] | |||
[[Category: Goay SSM]] | |||
[[Category: Jian S]] | |||
[[Category: Ong ST]] | |||
[[Category: Tian C]] | |||
[[Category: Tyagi A]] | |||
[[Category: Vorobyov I]] | |||
[[Category: Zhao Y]] | |||
Latest revision as of 14:41, 23 October 2024
Composite map of human Kv1.3 channel in dalazatide-bound state with beta subunitsComposite map of human Kv1.3 channel in dalazatide-bound state with beta subunits
Structural highlights
FunctionKCNA3_HUMAN Mediates the voltage-dependent potassium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a potassium-selective channel through which potassium ions may pass in accordance with their electrochemical gradient. Publication Abstract from PubMedWe report two structures of the human voltage-gated potassium channel (Kv) Kv1.3 in immune cells alone (apo-Kv1.3) and bound to an immunomodulatory drug called dalazatide (dalazatide-Kv1.3). Both the apo-Kv1.3 and dalazatide-Kv1.3 structures are in an activated state based on their depolarized voltage sensor and open inner gate. In apo-Kv1.3, the aromatic residue in the signature sequence (Y447) adopts a position that diverges 11 A from other K(+) channels. The outer pore is significantly rearranged, causing widening of the selectivity filter and perturbation of ion binding within the filter. This conformation is stabilized by a network of intrasubunit hydrogen bonds. In dalazatide-Kv1.3, binding of dalazatide to the channel's outer vestibule narrows the selectivity filter, Y447 occupies a position seen in other K(+) channels, and this conformation is stabilized by a network of intersubunit hydrogen bonds. These remarkable rearrangements in the selectivity filter underlie Kv1.3's transition into the drug-blocked state. Rearrangement of a unique Kv1.3 selectivity filter conformation upon binding of a drug.,Tyagi A, Ahmed T, Jian S, Bajaj S, Ong ST, Goay SSM, Zhao Y, Vorobyov I, Tian C, Chandy KG, Bhushan S Proc Natl Acad Sci U S A. 2022 Feb 1;119(5):e2113536119. doi: , 10.1073/pnas.2113536119. PMID:35091471[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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