7ssv: Difference between revisions
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==Structure of human Kv1.3 with Fab-ShK fusion== | ==Structure of human Kv1.3 with Fab-ShK fusion== | ||
<StructureSection load='7ssv' size='340' side='right'caption='[[7ssv]]' scene=''> | <StructureSection load='7ssv' size='340' side='right'caption='[[7ssv]], [[Resolution|resolution]] 3.39Å' 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=7SSV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7SSV FirstGlance]. <br> | <table><tr><td colspan='2'>[[7ssv]] is a 6 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7SSV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7SSV 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=7ssv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ssv OCA], [https://pdbe.org/7ssv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ssv RCSB], [https://www.ebi.ac.uk/pdbsum/7ssv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ssv ProSAT]</span></td></tr> | </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=7ssv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ssv OCA], [https://pdbe.org/7ssv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ssv RCSB], [https://www.ebi.ac.uk/pdbsum/7ssv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ssv 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 == | |||
The Kv1.3 potassium channel is expressed abundantly on activated T cells and mediates the cellular immune response. This role has made the channel a target for therapeutic immunomodulation to block its activity and suppress T cell activation. Here, we report structures of human Kv1.3 alone, with a nanobody inhibitor, and with an antibody-toxin fusion blocker. Rather than block the channel directly, four copies of the nanobody bind the tetramer's voltage sensing domains and the pore domain to induce an inactive pore conformation. In contrast, the antibody-toxin fusion docks its toxin domain at the extracellular mouth of the channel to insert a critical lysine into the pore. The lysine stabilizes an active conformation of the pore yet blocks ion permeation. This study visualizes Kv1.3 pore dynamics, defines two distinct mechanisms to suppress Kv1.3 channel activity with exogenous inhibitors, and provides a framework to aid development of emerging T cell immunotherapies. | |||
Structures of the T cell potassium channel Kv1.3 with immunoglobulin modulators.,Selvakumar P, Fernandez-Marino AI, Khanra N, He C, Paquette AJ, Wang B, Huang R, Smider VV, Rice WJ, Swartz KJ, Meyerson JR Nat Commun. 2022 Jul 4;13(1):3854. doi: 10.1038/s41467-022-31285-5. PMID:35788586<ref>PMID:35788586</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 7ssv" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Meyerson, | [[Category: Huang, R]] | ||
[[Category: Meyerson, J R]] | |||
[[Category: Selvakumar, P]] | |||
[[Category: Smider, V]] | |||
[[Category: Immune system]] | |||
[[Category: Ion channel]] | |||