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@ARTICLE{Govorunova:943338,
author = {Govorunova, Elena G. and Sineshchekov, Oleg A. and Brown,
Leonid S. and Bondar, Ana-Nicoleta and Spudich, John L.},
title = {{S}tructural {F}oundations of {P}otassium {S}electivity in
{C}hannelrhodopsins},
journal = {mBio},
volume = {13},
number = {6},
issn = {2161-2129},
address = {Washington, DC},
publisher = {American Society for Microbiology},
reportid = {FZJ-2023-00944},
pages = {e03039-22},
year = {2022},
abstract = {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.},
cin = {IAS-5 / INM-9},
ddc = {570},
cid = {I:(DE-Juel1)IAS-5-20120330 / I:(DE-Juel1)INM-9-20140121},
pnm = {5241 - Molecular Information Processing in Cellular Systems
(POF4-524)},
pid = {G:(DE-HGF)POF4-5241},
typ = {PUB:(DE-HGF)16},
pubmed = {36413022},
UT = {WOS:000890586800001},
doi = {10.1128/mbio.03039-22},
url = {https://juser.fz-juelich.de/record/943338},
}