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PreprintCited by 18Photoreceptor and optogenetics researchReceptor Mechanisms and SignalingIon channel regulation and function

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A novel subgroup of light-driven sodium pumps with an additional Schiff base counterion

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Podoliak, E., Lamm, G. H. U., Alekseev, A., Marin, E., Schellbach, A. V., Fedotov, D. A., Stetsenko, A., Maliar, N., Bourenkov, G., Balandin, T., Baeken, C., Astashkin, R., Schneider, T. R., Bateman, A., Wachtveitl, J., Schapiro, I., Busskamp, V., Guskov, A., Gordeliy, V., Kovalev, K.·2023·Nature Communications
DOI 10.1101/2023.10.11.561842PMC PMC11006869

Preprint — published as 10.1038/s41467-024-47469-0

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Abstract

Light-driven sodium pumps (NaRs) are unique ion-transporting microbial rhodopsins. The major group of NaRs is characterized by an NDQ motif and has two aspartic acid residues in the central region essential for sodium transport. Here we identified a new subgroup of the NDQ rhodopsins bearing an additional glutamic acid residue in the close vicinity to the retinal Schiff base. We thoroughly characterized a member of this subgroup, namely the protein Er NaR from Erythrobacter sp. HL-111 and showed that the additional glutamic acid results in almost complete loss of pH sensitivity for sodium-pumping activity, which is in contrast to previously studied NaRs. Er NaR is capable of transporting sodium efficiently even at acidic pH levels. X-ray crystallography and single particle cryo-electron microscopy reveal that the additional glutamic acid residue mediates the connection between the other two Schiff base counterions and strongly interacts with the aspartic acid of the characteristic NDQ motif. Hence, it reduces its pKa. Our findings shed light on a new subgroup of NaRs and might serve as a basis for their rational optimization for optogenetics.

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Metadata

Authors
Podoliak, E., Lamm, G. H. U., Alekseev, A., Marin, E., Schellbach, A. V., Fedotov, D. A., Stetsenko, A., Maliar, N., Bourenkov, G., Balandin, T., Baeken, C., Astashkin, R., Schneider, T. R., Bateman, A., Wachtveitl, J., Schapiro, I., Busskamp, V., Guskov, A., Gordeliy, V., & Kovalev, K.
Affiliations
  • University Hospital Bonn (DE)
  • Goethe University Frankfurt (DE)
  • Universitätsmedizin Göttingen (DE)
  • University of Groningen (NL)
  • Hebrew University of Jerusalem (IL)
  • University of Cambridge (GB)
  • Deutsches Elektronen-Synchrotron DESY (DE)
  • Forschungszentrum Jülich (DE)
  • Centre National de la Recherche Scientifique (FR)
  • European Bioinformatics Institute (GB)
Corresponding author
  • Alekseev, A.
  • Kovalev, K.
ORCID
Venue
Nature Communications
Publisher
openRxiv
Published
2023-10-12
Volume
15
Issue
1
Pages
3119-3119
ISSN
2041-1723 (ISSN-L)
DOI
10.1101/2023.10.11.561842
PMC
PMC11006869
OpenAlex
W4394674430
Cited by
18
References
1
Citations by year
2026: 6 · 2025: 5 · 2024: 7
FWCI
3.14
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Nature Communications (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • GoeScholar The Publication Server of the Georg-August-Universität Göttingen (Georg-August-Universität Göttingen) (publishedVersion, cc-by)
  • University of Groningen research database (University of Groningen / Centre for Information Technology) (publishedVersion, cc-by)
  • GoeScholar The Publication Server of the Georg-August-Universität Göttingen (Georg-August-Universität Göttingen) (submittedVersion, other-oa)
  • Apollo (University of Cambridge) (submittedVersion, cc-by)
  • RePEc: Research Papers in Economics (submittedVersion)
  • Desy Publications Database (Deutsches Elektronen-Synchrotron DESY) (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Publication Server of Goethe University Frankfurt am Main (Goethe University Frankfurt) (submittedVersion, cc-by-nc-nd)
Funders
  • European Commission (847543)
  • Deutsche Forschungsgemeinschaft (EXC 2067, EXC2151390873048, CRC 1078, CRC1507, EXC 2067‐1, 390729940, EXC 2067/1390729940, 390873048)
  • Volkswagen Foundation (Freigeist—A110720, A110720)
  • Bundesministerium für Bildung und Forschung (01EO2107)
  • Nederlandse Organisatie voor Wetenschappelijk Onderzoek (184.034.014, OCENW.KLEIN.141)
  • Rheinische Friedrich-Wilhelms-Universität Bonn
  • HORIZON EUROPE Marie Sklodowska-Curie Actions (847543)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Photoreceptor and optogenetics research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
Keywords
microbial rhodopsins, retinal Schiff base, glutamate residues, pH sensitivity, sodium transport, optogenetics, ion transport
MeSH terms
Sodium-Potassium-Exchanging ATPase, Aspartic Acid, Rhodopsin, Schiff Bases, Sodium, Glutamic Acid, Cryoelectron Microscopy, Rhodopsins, Microbial

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