8H86
Cryo-EM structure of the potassium-selective channelrhodopsin HcKCR1 in lipid nanodisc
Summary for 8H86
| Entry DOI | 10.2210/pdb8h86/pdb |
| EMDB information | 34530 |
| Descriptor | HcKCR1, RETINAL, (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, ... (5 entities in total) |
| Functional Keywords | membrane protein, cryo-em |
| Biological source | Hyphochytrium catenoides |
| Total number of polymer chains | 1 |
| Total formula weight | 40557.00 |
| Authors | Tajima, S.,Kim, Y.,Yamashita, K.,Fukuda, M.,Deisseroth, K.,Kato, H.E. (deposition date: 2022-10-21, release date: 2023-09-06, Last modification date: 2024-10-23) |
| Primary citation | Tajima, S.,Kim, Y.S.,Fukuda, M.,Jo, Y.,Wang, P.Y.,Paggi, J.M.,Inoue, M.,Byrne, E.F.X.,Kishi, K.E.,Nakamura, S.,Ramakrishnan, C.,Takaramoto, S.,Nagata, T.,Konno, M.,Sugiura, M.,Katayama, K.,Matsui, T.E.,Yamashita, K.,Kim, S.,Ikeda, H.,Kim, J.,Kandori, H.,Dror, R.O.,Inoue, K.,Deisseroth, K.,Kato, H.E. Structural basis for ion selectivity in potassium-selective channelrhodopsins. Cell, 186:4325-4344.e26, 2023 Cited by PubMed Abstract: 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 Å 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. PubMed: 37652010DOI: 10.1016/j.cell.2023.08.009 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (2.56 Å) |
Structure validation
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