title: Structure of the light-driven sodium pump KR2 and its implications for optogenetics.
abstract: A key and common process present in organisms from all domains of life is the maintenance of the ion gradient between the inside and the outside of the cell. The gradient is generated by various active transporters, among which are the light-driven ion pumps of the microbial rhodopsin family. Whereas the proton-pumping and anion-pumping rhodopsins have been known for a long time, the cation (sodium) pumps were described only recently. Following the discovery, high-resolution atomic structures of the pump KR2 were determined that revealed the complete ion translocation pathway, including the positions of the characteristic Asn-Asp-Gln (NDQ) triad, the unusual ion uptake cavity acting as a selectivity filter, the unique N-terminal α-helix, capping the ion release cavity, and unexpected flexibility of the retinal-binding pocket. The structures also revealed pentamerization of KR2 and binding of sodium ions at the interface. Finally, on the basis of the structures, potassium-pumping KR2 variants have been designed, making the findings even more important for optogenetic applications. In this Structural Snapshot, we analyse the implications of the structural findings for understanding the sodium translocation mechanism and application of the pump and its mutants in optogenetics.
authors.affiliation: Institute of Complex Systems (ICS), ICS-6: Structural Biochemistry, Research Centre Jülich, Germany.|Moscow Institute of Physics and Technology, Dolgoprudniy, Russia.
authors.forename: Ivan
authors.initials: I
authors.lastname: Gushchin
authors.affiliation: Institute of Complex Systems (ICS), ICS-6: Structural Biochemistry, Research Centre Jülich, Germany.|Moscow Institute of Physics and Technology, Dolgoprudniy, Russia.
authors.forename: Vitaly
authors.initials: V
authors.lastname: Shevchenko
authors.affiliation: Institute of Complex Systems (ICS), ICS-6: Structural Biochemistry, Research Centre Jülich, Germany.|Moscow Institute of Physics and Technology, Dolgoprudniy, Russia.|Institut de Biologie Structurale, Université Grenoble Alpes, France.|Institut de Biologie Structurale, Centre National de la Recherche Scientifique, Grenoble, France.|Institut de Biologie Structurale, Direction des Sciences du Vivant, Commissariat à l'Énergie Atomique, Grenoble, France.
authors.forename: Vitaly
authors.initials: V
authors.lastname: Polovinkin
authors.affiliation: Institute of Complex Systems (ICS), ICS-6: Structural Biochemistry, Research Centre Jülich, Germany.|Moscow Institute of Physics and Technology, Dolgoprudniy, Russia.
authors.forename: Valentin
authors.initials: V
authors.lastname: Borshchevskiy
authors.affiliation: Moscow Institute of Physics and Technology, Dolgoprudniy, Russia.
authors.forename: Pavel
authors.initials: P
authors.lastname: Buslaev
authors.affiliation: Max Planck Institute of Biophysics, Frankfurt am Main, Germany.
authors.forename: Ernst
authors.initials: E
authors.lastname: Bamberg
authors.affiliation: Institute of Complex Systems (ICS), ICS-6: Structural Biochemistry, Research Centre Jülich, Germany.|Moscow Institute of Physics and Technology, Dolgoprudniy, Russia.|Institut de Biologie Structurale, Université Grenoble Alpes, France.|Institut de Biologie Structurale, Centre National de la Recherche Scientifique, Grenoble, France.|Institut de Biologie Structurale, Direction des Sciences du Vivant, Commissariat à l'Énergie Atomique, Grenoble, France.
authors.forename: Valentin
authors.initials: V
authors.lastname: Gordeliy
mesh_terms: D001665:Binding Sites / Q000235:genetics; D018360:Crystallography, X-Ray; D017136:Ion Transport / Q000528:radiation effects; D008027:Light; D008956:Models, Chemical; D008958:Models, Molecular; D009154:Mutation; D010782:Photolysis / Q000528:radiation effects; D015202:Protein Engineering / Q000379:methods; D055503:Protein Multimerization; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D012964:Sodium / Q000737:chemistry / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
chemical_list: D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase
keywords: crystal structure; light-driven; microbial rhodopsins; optogenetics tools; potassium pump; sodium pump