8dfl: Difference between revisions
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=8dfl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8dfl OCA], [https://pdbe.org/8dfl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8dfl RCSB], [https://www.ebi.ac.uk/pdbsum/8dfl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8dfl ProSAT]</span></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=8dfl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8dfl OCA], [https://pdbe.org/8dfl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8dfl RCSB], [https://www.ebi.ac.uk/pdbsum/8dfl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8dfl ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== | <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 8dfl" style="background-color:#fffaf0;"></div> | |||
==See Also== | ==See Also== | ||
*[[Green Fluorescent Protein 3D structures|Green Fluorescent Protein 3D structures]] | *[[Green Fluorescent Protein 3D structures|Green Fluorescent Protein 3D structures]] | ||
*[[Potassium channel 3D structures|Potassium channel 3D structures]] | *[[Potassium channel 3D structures|Potassium channel 3D structures]] | ||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
Latest revision as of 12:33, 17 October 2024
Structure of human Kv1.3 with A0194009G09 nanobodies (alternate conformation)Structure of human Kv1.3 with A0194009G09 nanobodies (alternate conformation)
Structural highlights
Publication Abstract from PubMedThe 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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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