View source for 7ssy


==Structure of human Kv1.3 (alternate conformation)==
<StructureSection load='7ssy' size='340' side='right'caption='[[7ssy]], [[Resolution|resolution]] 2.89&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7ssy]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Aequorea_victoria Aequorea victoria] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7SSY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7SSY FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 2.89&#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=7ssy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ssy OCA], [https://pdbe.org/7ssy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ssy RCSB], [https://www.ebi.ac.uk/pdbsum/7ssy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ssy ProSAT]</span></td></tr>
</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.[https://www.uniprot.org/uniprot/GFP_AEQVI GFP_AEQVI] Energy-transfer acceptor. Its role is to transduce the blue chemiluminescence of the protein aequorin into green fluorescent light by energy transfer. Fluoresces in vivo upon receiving energy from the Ca(2+)-activated photoprotein aequorin.
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== 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&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 7ssy" style="background-color:#fffaf0;"></div>

==See Also==
*[[Green Fluorescent Protein 3D structures|Green Fluorescent Protein 3D structures]]
*[[Potassium channel 3D structures|Potassium channel 3D structures]]
== References ==
<references/>
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</StructureSection>
[[Category: Aequorea victoria]]
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Meyerson JR]]
[[Category: Selvakumar P]]