An Atomistic Model of a Precursor State of Light-Induced Channel Opening of Channelrhodopsin

Overview

Journal Biophys J

Publisher Cell Press

Specialty Biophysics

Date 2018 Sep 22

PMID 30236783

Citations 6

Authors

Cheng Cheng

Motoshi Kamiya

Mizuki Takemoto

Ryuichiro Ishitani

Osamu Nureki

Norio Yoshida

Shigehiko Hayashi

Affiliations

Soon will be listed here.

Abstract

Channelrhodopsins (ChRs) are microbial light-gated ion channels with a retinal chromophore and are widely utilized in optogenetics to precisely control neuronal activity with light. Despite increasing understanding of their structures and photoactivation kinetics, the atomistic mechanism of light gating and ion conduction remains elusive. Here, we present an atomic structural model of a chimeric ChR in a precursor state of the channel opening determined by an accurate hybrid molecular simulation technique and a statistical theory of internal water distribution. The photoactivated structure features extensive tilt of the chromophore accompanied by redistribution of water molecules in its binding pocket, which is absent in previously known photoactivated structures of analogous photoreceptors, and widely agrees with structural and spectroscopic experimental evidence of ChRs. The atomistic model manifests a photoactivated ion-conduction pathway that is markedly different from a previously proposed one and successfully explains experimentally observed mutagenic effects on key channel properties.

Citing Articles

Structural Insights Into the Opening Mechanism of C1C2 Channelrhodopsin.

Mulder M, Hwang S, Broser M, Brunle S, Skopintsev P, Schattenberg C J Am Chem Soc. 2024; 147(1):1282-1290.

PMID: 39680650 PMC: 11726564. DOI: 10.1021/jacs.4c15402.

Metadynamics simulations reveal mechanisms of Na+ and Ca2+ transport in two open states of the channelrhodopsin chimera, C1C2.

Prignano L, Stevens M, Vanegas J, Rempe S, Dempski R PLoS One. 2024; 19(9):e0309553.

PMID: 39241014 PMC: 11379304. DOI: 10.1371/journal.pone.0309553.

Properties of a Single Amino Acid Residue in the Third Transmembrane Domain Determine the Kinetics of Ambient Light-Sensitive Channelrhodopsin.

Hatakeyama A, Sugano E, Sayama T, Watanabe Y, Suzuki T, Tabata K Int J Mol Sci. 2023; 24(5).

PMID: 36902480 PMC: 10003734. DOI: 10.3390/ijms24055054.

Effects of External Perturbations on Protein Systems: A Microscopic View.

Dutta P, Roy P, Sengupta N ACS Omega. 2022; 7(49):44556-44572.

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The effect on ion channel of different protonation states of E90 in channelrhodopsin-2: a molecular dynamics simulation.

Cheng J, Zhang W, Zhou S, Ran X, Shang Y, Lo G RSC Adv. 2022; 11(24):14542-14551.

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