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| 001 | 943338 | ||
| 005 | 20240625095119.0 | ||
| 024 | 7 | _ | |a 10.1128/mbio.03039-22 |2 doi |
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| 100 | 1 | _ | |a Govorunova, Elena G. |0 P:(DE-HGF)0 |b 0 |
| 245 | _ | _ | |a Structural Foundations of Potassium Selectivity in Channelrhodopsins |
| 260 | _ | _ | |a Washington, DC |c 2022 |b American Society for Microbiology |
| 336 | 7 | _ | |a article |2 DRIVER |
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| 520 | _ | _ | |a Potassium-selective channelrhodopsins (KCRs) are light-gated K+ channels recently found in the stramenopile protist Hyphochytrium catenoides. When expressed in neurons, KCRs enable high-precision optical inhibition of spiking (optogenetic silencing). KCRs are capable of discriminating K+ from Na+ without the conventional K+ selectivity filter found in classical K+ channels. The genome of H. catenoides also encodes a third paralog that is more permeable for Na+ than for K+. To identify structural motifs responsible for the unusual K+ selectivity of KCRs, we systematically analyzed a series of chimeras and mutants of this protein. We found that mutations of three critical residues in the paralog convert its Na+-selective channel into a K+-selective one. Our characterization of homologous proteins from other protists (Colponema vietnamica, Cafeteria burkhardae, and Chromera velia) and metagenomic samples confirmed the importance of these residues for K+ selectivity. We also show that Trp102 and Asp116, conserved in all three H. catenoides paralogs, are necessary, although not sufficient, for K+ selectivity. Our results provide the foundation for further engineering of KCRs for optogenetic needs. |
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| 542 | _ | _ | |i 2022-12-20 |2 Crossref |u https://creativecommons.org/licenses/by/4.0/ |
| 542 | _ | _ | |i 2022-12-20 |2 Crossref |u https://journals.asm.org/non-commercial-tdm-license |
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| 700 | 1 | _ | |a Sineshchekov, Oleg A. |0 P:(DE-HGF)0 |b 1 |
| 700 | 1 | _ | |a Brown, Leonid S. |0 P:(DE-HGF)0 |b 2 |
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| 700 | 1 | _ | |a Spudich, John L. |0 P:(DE-HGF)0 |b 4 |e Corresponding author |
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| 856 | 4 | _ | |u https://juser.fz-juelich.de/record/943338/files/Govorunova_mBio2022.docx |y OpenAccess |
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