8h86: Difference between revisions
New page: '''Unreleased structure''' The entry 8h86 is ON HOLD Authors: Description: Category: Unreleased Structures |
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==Cryo-EM structure of the potassium-selective channelrhodopsin HcKCR1 in lipid nanodisc== | |||
<StructureSection load='8h86' size='340' side='right'caption='[[8h86]], [[Resolution|resolution]] 2.56Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[8h86]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Hyphochytrium_catenoides Hyphochytrium catenoides]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8H86 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8H86 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]] 2.56Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PLM:PALMITIC+ACID'>PLM</scene>, <scene name='pdbligand=PSC:(7R,17E,20E)-4-HYDROXY-N,N,N-TRIMETHYL-9-OXO-7-[(PALMITOYLOXY)METHYL]-3,5,8-TRIOXA-4-PHOSPHAHEXACOSA-17,20-DIEN-1-AMINIUM+4-OXIDE'>PSC</scene>, <scene name='pdbligand=RET:RETINAL'>RET</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=8h86 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8h86 OCA], [https://pdbe.org/8h86 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8h86 RCSB], [https://www.ebi.ac.uk/pdbsum/8h86 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8h86 ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
KCR channelrhodopsins (K(+)-selective light-gated ion channels) have received attention as potential inhibitory optogenetic tools but more broadly pose a fundamental mystery regarding how their K(+) selectivity is achieved. Here, we present 2.5-2.7 A cryo-electron microscopy structures of HcKCR1 and HcKCR2 and of a structure-guided mutant with enhanced K(+) selectivity. Structural, electrophysiological, computational, spectroscopic, and biochemical analyses reveal a distinctive mechanism for K(+) selectivity; rather than forming the symmetrical filter of canonical K(+) channels achieving both selectivity and dehydration, instead, three extracellular-vestibule residues within each monomer form a flexible asymmetric selectivity gate, while a distinct dehydration pathway extends intracellularly. Structural comparisons reveal a retinal-binding pocket that induces retinal rotation (accounting for HcKCR1/HcKCR2 spectral differences), and design of corresponding KCR variants with increased K(+) selectivity (KALI-1/KALI-2) provides key advantages for optogenetic inhibition in vitro and in vivo. Thus, discovery of a mechanism for ion-channel K(+) selectivity also provides a framework for next-generation optogenetics. | |||
Structural basis for ion selectivity in potassium-selective channelrhodopsins.,Tajima S, Kim YS, Fukuda M, Jo Y, Wang PY, Paggi JM, Inoue M, Byrne EFX, Kishi KE, Nakamura S, Ramakrishnan C, Takaramoto S, Nagata T, Konno M, Sugiura M, Katayama K, Matsui TE, Yamashita K, Kim S, Ikeda H, Kim J, Kandori H, Dror RO, Inoue K, Deisseroth K, Kato HE Cell. 2023 Sep 28;186(20):4325-4344.e26. doi: 10.1016/j.cell.2023.08.009. Epub , 2023 Aug 30. PMID:37652010<ref>PMID:37652010</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 8h86" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Hyphochytrium catenoides]] | |||
[[Category: Large Structures]] | |||
[[Category: Deisseroth K]] | |||
[[Category: Fukuda M]] | |||
[[Category: Kato HE]] | |||
[[Category: Kim Y]] | |||
[[Category: Tajima S]] | |||
[[Category: Yamashita K]] | |||
Latest revision as of 15:13, 23 October 2024
Cryo-EM structure of the potassium-selective channelrhodopsin HcKCR1 in lipid nanodiscCryo-EM structure of the potassium-selective channelrhodopsin HcKCR1 in lipid nanodisc
Structural highlights
Publication Abstract from PubMedKCR channelrhodopsins (K(+)-selective light-gated ion channels) have received attention as potential inhibitory optogenetic tools but more broadly pose a fundamental mystery regarding how their K(+) selectivity is achieved. Here, we present 2.5-2.7 A cryo-electron microscopy structures of HcKCR1 and HcKCR2 and of a structure-guided mutant with enhanced K(+) selectivity. Structural, electrophysiological, computational, spectroscopic, and biochemical analyses reveal a distinctive mechanism for K(+) selectivity; rather than forming the symmetrical filter of canonical K(+) channels achieving both selectivity and dehydration, instead, three extracellular-vestibule residues within each monomer form a flexible asymmetric selectivity gate, while a distinct dehydration pathway extends intracellularly. Structural comparisons reveal a retinal-binding pocket that induces retinal rotation (accounting for HcKCR1/HcKCR2 spectral differences), and design of corresponding KCR variants with increased K(+) selectivity (KALI-1/KALI-2) provides key advantages for optogenetic inhibition in vitro and in vivo. Thus, discovery of a mechanism for ion-channel K(+) selectivity also provides a framework for next-generation optogenetics. Structural basis for ion selectivity in potassium-selective channelrhodopsins.,Tajima S, Kim YS, Fukuda M, Jo Y, Wang PY, Paggi JM, Inoue M, Byrne EFX, Kishi KE, Nakamura S, Ramakrishnan C, Takaramoto S, Nagata T, Konno M, Sugiura M, Katayama K, Matsui TE, Yamashita K, Kim S, Ikeda H, Kim J, Kandori H, Dror RO, Inoue K, Deisseroth K, Kato HE Cell. 2023 Sep 28;186(20):4325-4344.e26. doi: 10.1016/j.cell.2023.08.009. Epub , 2023 Aug 30. PMID:37652010[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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