ArticleProceedings of the National Academy of Sciences of the United States of America2013
Transient protonation changes in channelrhodopsin-2 and their relevance to channel gating.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers.
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69 citing papers in PubMed, 167 citations in OpenAlex.
- The Human Circadian Clock Protein Cryptochrome-1 Responds to Photochemistry by Conformational Changes.Journal of the American Chemical Society · 2026Article
- A second photoactivatable state of the anion-conducting channelrhodopsin GtACR1 empowers persistent activity.Communications biology · 2025Article
- Ion-conducting and gating molecular mechanisms of channelrhodopsin revealed by true-atomic-resolution structures of open and closed states.Nature structural & molecular biology · 2025Article
- Pore-Opening and Ion-Conduction Mechanism in Channelrhodopsins C1C2, ChR2, and iChloC by Computational Electrophysiology and Constant-pH Simulations.Journal of chemical information and modeling · 2025Article
- Combined Mutational and Spectroscopic Study on the Calcium-Related Kinetic Effects on the VirChR1 Photocycle.The journal of physical chemistry. B · 2025Article
- Structural Insights Into the Opening Mechanism of C1C2 Channelrhodopsin.Journal of the American Chemical Society · 2025Article
- FTIR study of the wild-type and mutant proteins of a viral rhodopsin, OLPVR1.Biophysics and physicobiology · 2025Article
- Characterization of the tail current of Channelrhodopsin-2 variants.Biochemistry and biophysics reports · 2024Article
- Channel Gating in Kalium Channelrhodopsin Slow Mutants.Journal of molecular biology · 2024Article
- Metadynamics simulations reveal mechanisms of Na+ and Ca2+ transport in two open states of the channelrhodopsin chimera, C1C2.PloS one · 2024Article
- Potassium-selective channelrhodopsins.Biophysics and physicobiology · 2023Article
- Algal rhodopsins encoding diverse signal sequence holds potential for expansion of organelle optogenetics.Biophysics and physicobiology · 2023Article
- The Mechanism of the Channel Opening in Channelrhodopsin-2: A Molecular Dynamics Simulation.International journal of molecular sciences · 2023Article
- Time-resolved photoacoustics of channelrhodopsins: early energetics and light-driven volume changes.Photochemical & photobiological sciences : Official journal of the European Photochemistry Association and the European Society for Photobiology · 2023Article
- Cryo-EM structures of the channelrhodopsin ChRmine in lipid nanodiscs.Nature communications · 2022Article
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- Modeling theRSC advances · 2022Article
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- Rhodopsin-Based Optogenetics: Basics and Applications.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Article
9 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The discovery of the light-gated ion channel channelrhodopsin (ChR) set the stage for the novel field of optogenetics, where cellular processes are controlled by light. However, the underlying molecular mechanism of light-induced cation permeation in ChR2 remains unknown. Here, we have traced the structural changes of ChR2 by time-resolved FTIR spectroscopy, complemented by functional electrophysiological measurements. We have resolved the vibrational changes associated with the open states of the channel (P(2)(390) and P(3)(520)) and characterized several proton transfer events. Analysis of the amide I vibrations suggests a transient increase in hydration of transmembrane α-helices with a t(1/2) = 60 μs, which tallies with the onset of cation permeation. Aspartate 253 accepts the proton released by the Schiff base (t(1/2) = 10 μs), with the latter being reprotonated by aspartic acid 156 (t(1/2) = 2 ms). The internal proton acceptor and donor groups, corresponding to D212 and D115 in bacteriorhodopsin, are clearly different from other microbial rhodopsins, indicating that their spatial position in the protein was relocated during evolution. Previous conclusions on the involvement of glutamic acid 90 in channel opening are ruled out by demonstrating that E90 deprotonates exclusively in the nonconductive P(4)(480) state. Our results merge into a mechanistic proposal that relates the observed proton transfer reactions and the protein conformational changes to the gating of the cation channel.
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