A generic residue-numbering system for microbial rhodopsins.
13 affiliations
- 1Condensed Matter Theory Group, PSI Center for Scientific Computing, Theory and Data, Villigen-PSI, Switzerland.
- 2Department of Biology, ETH Zürich, Zürich, Switzerland.
- 3Swiss Institute of Bioinformatics (SIB), Lausanne, Switzerland.
- 4Research Center for Advanced Science and Technology, The University of Tokyo, Meguro, Tokyo Japan.
- 5Department of Life Sciences, School of Arts and Sciences, The University of Tokyo, Meguro, Tokyo Japan.
- 6Atmosphere and Ocean Research Institute, The University of Tokyo, Chiba, Japan.
- 7Institute for Extra-cutting-edge Science and Technology Avant-garde Research of Life (X-star), Japan Agency for Marine-Earth Science and Technology (JAMSTEC), Kanagawa, Japan.
- 8Graduate School of Frontier Sciences, The University of Tokyo, Chiba, Japan.
- 9Collaborative Research Institute for Innovative Microbiology, The University of Tokyo, Tokyo, Japan.
- 10Laboratory of Biomolecular Research, PSI Center for Life Sciences, Villigen-PSI, Switzerland.
- 11Department of Biological Sciences, Graduate School of Science, The University of Tokyo, Bunkyo, Tokyo Japan.
- 12FOREST, Japan Science and Technology Agency, Kawaguchi, Saitama Japan.
- 13CREST, Japan Science and Technology Agency, Kawaguchi, Saitama Japan.
Abstract
Microbial rhodopsins are photoreceptors with a conserved seven-transmembrane core architecture that use the chromophore retinal-a vitamin A derivative-to convert light absorption into ion transport, signaling, and enzymatic activity. Since their discovery half a century ago, genome sequencing has uncovered thousands of these proteins across archaea, bacteria, eukaryotes, and viruses, revealing a diverse functional repertoire that includes ion pumps and channels, transducer activators, and enzyme/channel regulators. Although the structure of the seven-transmembrane bundle core and the retinal-binding pocket is highly conserved, the sequence identity across major classes is low. This low sequence identity, combined with the rapidly expanding number of microbial rhodopsins identified by metagenomics, makes direct comparisons across the superfamily increasingly difficult. Here, we introduce a generic residue-numbering system for microbial rhodopsins (MO numbering system), a structure-guided framework anchored to the retinal-binding pocket that enables consistent residue comparison across even the most divergent family members. Analyzing 129 structures and approximately 40,000 sequences, we demonstrate its utility by analyzing sequence-structure-function relationships across the superfamily, including previously uncharacterized members. The MO numbering system provides a common language for organizing the growing repertoire of microbial rhodopsins, integrating structural, spectroscopic, and electrophysiological data, and engineering next-generation optogenetic tools.
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BibTeX
@article{hidber2026generic,
title = {{A generic residue-numbering system for microbial rhodopsins.}},
author = {Flurin S Hidber and Seiya Tajima and Koichiro E Kishi and Yosuke Nishimura and Susumu Yoshizawa and Xavier Deupi and Hideaki E Kato},
journal = {Npj structural biology},
year = {2026},
month = nov,
doi = {10.1038/s44511-026-00004-w},
url = {https://europepmc.org/article/MED/42996294},
note = {CC BY},
}
RIS
TY - JOUR
TI - A generic residue-numbering system for microbial rhodopsins.
AU - Flurin S Hidber
AU - Seiya Tajima
AU - Koichiro E Kishi
AU - Yosuke Nishimura
AU - Susumu Yoshizawa
AU - Xavier Deupi
AU - Hideaki E Kato
PY - 2026
DA - 2026/11/05
JO - Npj structural biology
DO - 10.1038/s44511-026-00004-w
UR - https://europepmc.org/article/MED/42996294
AB - Microbial rhodopsins are photoreceptors with a conserved seven-transmembrane core architecture that use the chromophore retinal-a vitamin A derivative-to convert light absorption into ion transport, signaling, and enzymatic activity. Since their discovery half a century ago, genome sequencing has uncovered thousands of these proteins across archaea, bacteria, eukaryotes, and viruses, revealing a diverse functional repertoire that includes ion pumps and channels, transducer activators, and enzyme/channel regulators. Although the structure of the seven-transmembrane bundle core and the retinal-binding pocket is highly conserved, the sequence identity across major classes is low. This low sequence identity, combined with the rapidly expanding number of microbial rhodopsins identified by metagenomics, makes direct comparisons across the superfamily increasingly difficult. Here, we introduce a generic residue-numbering system for microbial rhodopsins (MO numbering system), a structure-guided framework anchored to the retinal-binding pocket that enables consistent residue comparison across even the most divergent family members. Analyzing 129 structures and approximately 40,000 sequences, we demonstrate its utility by analyzing sequence-structure-function relationships across the superfamily, including previously uncharacterized members. The MO numbering system provides a common language for organizing the growing repertoire of microbial rhodopsins, integrating structural, spectroscopic, and electrophysiological data, and engineering next-generation optogenetic tools.
SN - 3091-3888
ER -