title: Early formation of the ion-conducting pore in channelrhodopsin-2.
abstract: Channelrhodopsins (ChRs) are light-gated ion channels that are widely used in optogenetics. They allow precise control of neuronal activity with light, but a detailed understanding of how the channel is gated and the ions are conducted is still lacking. The recent determination of the X-ray structural model in the closed state marks an important milestone. Herein the open state structure is presented and the early formation of the ion conducting pore is elucidated in atomic detail using time-resolved FTIR spectroscopy. Photo-isomerization of the retinal-chromophore causes a downward movement of the highly conserved E90, which opens the pore. Molecular dynamic (MD) simulations show that water molecules invade through this opened pore, Helix 2 tilts and the channel fully opens within ms. Since E90 is a highly conserved residue, the proposed E90-Helix2-tilt (EHT) model might describe a general activation mechanism and provides a new avenue for further mechanistic studies and engineering.
authors.affiliation: Lehrstuhl für Biophysik, Ruhr Universität Bochum, Universitätsstrasse 150, 44780 Bochum (Germany).
authors.forename: Jens
authors.initials: J
authors.lastname: Kuhne
authors.forename: Kirstin
authors.initials: K
authors.lastname: Eisenhauer
authors.forename: Eglof
authors.initials: E
authors.lastname: Ritter
authors.forename: Peter
authors.initials: P
authors.lastname: Hegemann
authors.forename: Klaus
authors.initials: K
authors.lastname: Gerwert
authors.forename: Franz
authors.initials: F
authors.lastname: Bartl
mesh_terms: D007477:Ions / Q000737:chemistry; D056004:Molecular Dynamics Simulation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011522:Protons; D012243:Rhodopsin / Q000737:chemistry* / Q000378:metabolism; D012545:Schiff Bases / Q000737:chemistry; D013056:Spectrophotometry, Ultraviolet; D017550:Spectroscopy, Fourier Transform Infrared
chemical_list: D007477:Ions; D011522:Protons; D012545:Schiff Bases; D012243:Rhodopsin
keywords: IR spectroscopy; channelrhodopsin; molecular dynamics; optogenetics