8h86

Cryo-EM structure of the potassium-selective channelrhodopsin HcKCR1 in lipid nanodisc

spinqualitylabelsall models 8h86, resolution 2.56Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8h86 is a 1 chain structure with sequence from Hyphochytrium catenoides. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 2.56Å Ligands: PLM, PSC, RET Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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