A subgroup of light-driven sodium pumps with an additional Schiff base counterion
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 identify a subgroup of the NDQ rhodopsins bearing an a...
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Nature Portfolio
2024-04-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-47469-0 |
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| author | E. Podoliak G. H. U. Lamm E. Marin A. V. Schellbach D. A. Fedotov A. Stetsenko M. Asido N. Maliar G. Bourenkov T. Balandin C. Baeken R. Astashkin T. R. Schneider A. Bateman J. Wachtveitl I. Schapiro V. Busskamp A. Guskov V. Gordeliy A. Alekseev K. Kovalev |
| author_facet | E. Podoliak G. H. U. Lamm E. Marin A. V. Schellbach D. A. Fedotov A. Stetsenko M. Asido N. Maliar G. Bourenkov T. Balandin C. Baeken R. Astashkin T. R. Schneider A. Bateman J. Wachtveitl I. Schapiro V. Busskamp A. Guskov V. Gordeliy A. Alekseev K. Kovalev |
| author_sort | E. Podoliak |
| collection | DOAJ |
| description | 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 identify a subgroup of the NDQ rhodopsins bearing an additional glutamic acid residue in the close vicinity to the retinal Schiff base. We thoroughly characterize a member of this subgroup, namely the protein ErNaR from Erythrobacter sp. HL-111 and show 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. ErNaR 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 subgroup of NaRs and might serve as a basis for their rational optimization for optogenetics. |
| first_indexed | 2024-04-24T09:52:32Z |
| format | Article |
| id | doaj.art-bbafc15b03ac4530a1702ccc8d42a86e |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-04-24T09:52:32Z |
| publishDate | 2024-04-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-bbafc15b03ac4530a1702ccc8d42a86e2024-04-14T11:20:22ZengNature PortfolioNature Communications2041-17232024-04-0115111610.1038/s41467-024-47469-0A subgroup of light-driven sodium pumps with an additional Schiff base counterionE. Podoliak0G. H. U. Lamm1E. Marin2A. V. Schellbach3D. A. Fedotov4A. Stetsenko5M. Asido6N. Maliar7G. Bourenkov8T. Balandin9C. Baeken10R. Astashkin11T. R. Schneider12A. Bateman13J. Wachtveitl14I. Schapiro15V. Busskamp16A. Guskov17V. Gordeliy18A. Alekseev19K. Kovalev20Department of Ophthalmology, University Hospital Bonn, Medical FacultyInstitute of Physical and Theoretical Chemistry, Goethe University FrankfurtGroningen Institute for Biomolecular Sciences and Biotechnology, University of GroningenInstitute of Physical and Theoretical Chemistry, Goethe University FrankfurtFritz Haber Center for Molecular Dynamics Research, Institute of Chemistry, The Hebrew University of JerusalemGroningen Institute for Biomolecular Sciences and Biotechnology, University of GroningenInstitute of Physical and Theoretical Chemistry, Goethe University FrankfurtDepartment of Biochemistry, University of CambridgeEuropean Molecular Biology Laboratory, EMBL Hamburg c/o DESYInstitute of Biological Information Processing (IBI-7: Structural Biochemistry), Forschungszentrum JülichInstitute of Biological Information Processing (IBI-7: Structural Biochemistry), Forschungszentrum JülichUniv. Grenoble Alpes, CEA, CNRS, Institut de Biologie Structurale (IBS)European Molecular Biology Laboratory, EMBL Hamburg c/o DESYEuropean Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Wellcome Genome CampusInstitute of Physical and Theoretical Chemistry, Goethe University FrankfurtFritz Haber Center for Molecular Dynamics Research, Institute of Chemistry, The Hebrew University of JerusalemDepartment of Ophthalmology, University Hospital Bonn, Medical FacultyGroningen Institute for Biomolecular Sciences and Biotechnology, University of GroningenInstitute of Biological Information Processing (IBI-7: Structural Biochemistry), Forschungszentrum JülichUniversity Medical Center Göttingen, Institute for Auditory Neuroscience and InnerEarLabEuropean Molecular Biology Laboratory, EMBL Hamburg c/o DESYAbstract 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 identify a subgroup of the NDQ rhodopsins bearing an additional glutamic acid residue in the close vicinity to the retinal Schiff base. We thoroughly characterize a member of this subgroup, namely the protein ErNaR from Erythrobacter sp. HL-111 and show 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. ErNaR 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 subgroup of NaRs and might serve as a basis for their rational optimization for optogenetics.https://doi.org/10.1038/s41467-024-47469-0 |
| spellingShingle | E. Podoliak G. H. U. Lamm E. Marin A. V. Schellbach D. A. Fedotov A. Stetsenko M. Asido N. Maliar G. Bourenkov T. Balandin C. Baeken R. Astashkin T. R. Schneider A. Bateman J. Wachtveitl I. Schapiro V. Busskamp A. Guskov V. Gordeliy A. Alekseev K. Kovalev A subgroup of light-driven sodium pumps with an additional Schiff base counterion Nature Communications |
| title | A subgroup of light-driven sodium pumps with an additional Schiff base counterion |
| title_full | A subgroup of light-driven sodium pumps with an additional Schiff base counterion |
| title_fullStr | A subgroup of light-driven sodium pumps with an additional Schiff base counterion |
| title_full_unstemmed | A subgroup of light-driven sodium pumps with an additional Schiff base counterion |
| title_short | A subgroup of light-driven sodium pumps with an additional Schiff base counterion |
| title_sort | subgroup of light driven sodium pumps with an additional schiff base counterion |
| url | https://doi.org/10.1038/s41467-024-47469-0 |
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