Structure of the light‐driven sodium pump <scp>KR</scp>2 and its implications for optogenetics

<jats:p>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 <jats:styled-content style="fixed-case">KR</jats:styled-content>2 were determined that revealed the complete ion translocation pathway, including the positions of the characteristic Asn‐Asp‐Gln (<jats:styled-content style="fixed-case">NDQ</jats:styled-content>) 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 <jats:styled-content style="fixed-case">KR</jats:styled-content>2 and binding of sodium ions at the interface. Finally, on the basis of the structures, potassium‐pumping <jats:styled-content style="fixed-case">KR</jats:styled-content>2 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.</jats:p>