Inward H$^+$ pump xenorhodopsin: Mechanism and alternative optogenetic approach

Vitaly Shevchenko (1, 2, 3) , Thomas Mager (4) , Kirill Kovalev (3, 1, 2) , Vitaly Polovinkin (3, 1, 5) , Alexey Alekseev (1, 3, 2) , Josephine Juettner (6) , Igor Chizhov (7) , Christian Bamann (4) , Charlotte Vavourakis (8) , Rohit Ghai (9) , Ivan Yu. Gushchin (1, 3) , Valentin Borshchevskiy (3) , Andrey Rogachev (3, 10) , Igor Melnikov (11) , Alexander Popov (11) , Taras Balandin (1) , Francisco Rodriguez-Valera (12) , Dietmar Manstein (7) , Georg Bueldt (3) , Ernst Bamberg (4) , Valentin I. Gordeliy (3, 1, 5)

1 ICS - Institute of Complex Systems
2 Institute of Crystallography [Aachen]
3 MIPT - Moscow Institute of Physics and Technology [Moscow]
4 MPIBP - Max-Planck-Institut für Biophysik - Max Planck Institute of Biophysics
5 IBS - UMR 5075 - Institut de biologie structurale
6 FMI - Friedrich Miescher Institute for Biomedical Research
7 MHH - Hannover Medical School [Hannover]
8 UvA - University of Amsterdam [Amsterdam]
9 BIOLOGY CENTRE CAS - Biology Centre of the Czech Academy of Sciences
10 JINR - Joint Institute for Nuclear Research
11 ESRF - European Synchrotron Radiation Facility
12 UMH - Universidad Miguel Hernández [Elche]

Generation of an electrochemical proton gradient is the first step of cell bioenergetics. In prokaryotes, the gradient is created by outward membrane protein proton pumps. Inward plasma membrane native proton pumps are yet unknown. We describe comprehensive functional studies of the representatives of the yet noncharacterized xenorhodopsins from Nanohaloarchaea family of microbial rhodopsins. They are inward proton pumps as we demonstrate in model membrane systems, $Escherichia\ coli$ cells, human embryonic kidney cells, neuroblastoma cells, and rat hippocampal neuronal cells. We also solved the structure of a xenorhodopsin from the nanohalosarchaeon $Nanosalina$ (NsXeR) and suggest a mechanism of inward proton pumping. We demonstrate that the NsXeR is a powerful pump, which is able to elicit action potentials in rat hippocampal neuronal cells up to their maximal intrinsic firing frequency. Hence, inwardly directed proton pumps are suitable for light-induced remote control of neurons, and they are an alternative to the well-known cation-selective channelrhodopsins.

Domains: Life Sciences [q-bio]; Biological Physics [physics.bio-ph]

Vitaly Shevchenko, Thomas Mager, Kirill Kovalev, Vitaly Polovinkin, Alexey Alekseev, et al.. Inward H$^+$ pump xenorhodopsin: Mechanism and alternative optogenetic approach. Science Advances , 2017, 3 (9), pp.e1603187. ⟨10.1126/sciadv.1603187⟩. ⟨cea-01888660⟩