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Structural basis for ion selectivity in potassium-selective channelrhodopsins.
Tajima, Seiya; Kim, Yoon Seok; Fukuda, Masahiro; Jo, YoungJu; Wang, Peter Y; Paggi, Joseph M; Inoue, Masatoshi; Byrne, Eamon F X; Kishi, Koichiro E; Nakamura, Seiwa; Ramakrishnan, Charu; Takaramoto, Shunki; Nagata, Takashi; Konno, Masae; Sugiura, Masahiro; Katayama, Kota; Matsui, Toshiki E; Yamashita, Keitaro; Kim, Suhyang; Ikeda, Hisako; Kim, Jaeah; Kandori, Hideki; Dror, Ron O; Inoue, Keiichi; Deisseroth, Karl; Kato, Hideaki E.
Afiliación
  • Tajima S; Komaba Institute for Science, The University of Tokyo, Meguro, Tokyo, Japan.
  • Kim YS; Department of Bioengineering, Stanford University, Stanford, CA, USA.
  • Fukuda M; Komaba Institute for Science, The University of Tokyo, Meguro, Tokyo, Japan.
  • Jo Y; Department of Bioengineering, Stanford University, Stanford, CA, USA.
  • Wang PY; Department of Bioengineering, Stanford University, Stanford, CA, USA.
  • Paggi JM; Department of Computer Science, Stanford University, Stanford, CA, USA.
  • Inoue M; Department of Bioengineering, Stanford University, Stanford, CA, USA.
  • Byrne EFX; Department of Bioengineering, Stanford University, Stanford, CA, USA.
  • Kishi KE; Komaba Institute for Science, The University of Tokyo, Meguro, Tokyo, Japan.
  • Nakamura S; Komaba Institute for Science, The University of Tokyo, Meguro, Tokyo, Japan.
  • Ramakrishnan C; CNC Program, Stanford University, Stanford, CA, USA.
  • Takaramoto S; The Institute for Solid State Physics, The University of Tokyo, Kashiwa, Japan.
  • Nagata T; The Institute for Solid State Physics, The University of Tokyo, Kashiwa, Japan.
  • Konno M; The Institute for Solid State Physics, The University of Tokyo, Kashiwa, Japan; PRESTO, Japan Science and Technology Agency, Kawaguchi, Saitama, Japan.
  • Sugiura M; Department of Life Science and Applied Chemistry, Nagoya Institute of Technology, Showa-ku, Japan.
  • Katayama K; Department of Life Science and Applied Chemistry, Nagoya Institute of Technology, Showa-ku, Japan.
  • Matsui TE; Komaba Institute for Science, The University of Tokyo, Meguro, Tokyo, Japan.
  • Yamashita K; MRC Laboratory of Molecular Biology, Cambridge Biomedical Campus, Cambridge, UK.
  • Kim S; Komaba Institute for Science, The University of Tokyo, Meguro, Tokyo, Japan.
  • Ikeda H; Komaba Institute for Science, The University of Tokyo, Meguro, Tokyo, Japan.
  • Kim J; Department of Bioengineering, Stanford University, Stanford, CA, USA.
  • Kandori H; Department of Life Science and Applied Chemistry, Nagoya Institute of Technology, Showa-ku, Japan; OptoBioTechnology Research Center, Nagoya Institute of Technology, Showa-ku, Japan.
  • Dror RO; Department of Computer Science, Stanford University, Stanford, CA, USA; Institute for Computational and Mathematical Engineering, Stanford University, Stanford, CA, USA.
  • Inoue K; The Institute for Solid State Physics, The University of Tokyo, Kashiwa, Japan.
  • Deisseroth K; Department of Bioengineering, Stanford University, Stanford, CA, USA; CNC Program, Stanford University, Stanford, CA, USA; Howard Hughes Medical Institute, Stanford University, Stanford, CA, USA; Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA. Electronic add
  • Kato HE; Komaba Institute for Science, The University of Tokyo, Meguro, Tokyo, Japan; Department of Biological Sciences, Graduate School of Science, The University of Tokyo, Bunkyo, Tokyo, Japan; FOREST, Japan Science and Technology Agency, Kawaguchi, Saitama, Japan. Electronic address: hekato@bio.c.u-tokyo.
Cell ; 186(20): 4325-4344.e26, 2023 09 28.
Article en En | MEDLINE | ID: mdl-37652010
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Rhinosporidium / Channelrhodopsins Límite: Humans Idioma: En Revista: Cell Año: 2023 Tipo del documento: Article País de afiliación: Japón
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Rhinosporidium / Channelrhodopsins Límite: Humans Idioma: En Revista: Cell Año: 2023 Tipo del documento: Article País de afiliación: Japón