Nonadiabatic Photodynamics of Retinal Protonated Schiff Base in Channelrhodopsin 2

Liang, Ruibin; Liu, Fang; Martínez, Todd J.

doi:10.1021/acs.jpclett.9b00701

Title: Nonadiabatic Photodynamics of Retinal Protonated Schiff Base in Channelrhodopsin 2

Full Record
Other Related Research

Abstract

Channelrhodopsin 2 (ChR2) is a light-gated ion channel and an important tool in optogenetics. Photoisomerization of retinal protonated Schiff base (RPSB) in ChR2 triggers channel activation. Despite the importance of ChR2 in optogenetics, the detailed mechanism for photoisomerization and channel activation is still not fully understood. Here, we report on computer simulations to investigate the photoisomerization mechanism and its effect on the activation of ChR2. Nonadiabatic dynamics simulation of ChR2 was carried out using the ab initio multiple spawning (AIMS) method and quantum mechanics/molecular mechanics (QM/MM) with a restricted ensemble Kohn–Sham (REKS) treatment of the QM region. Our results agree well with spectroscopic measurements and reveal that the RPSB isomerization is highly specific around the C₁₃=C₁₄ bond and follows the “aborted bicycle-pedal” mechanism. In addition, RPSB photoisomerization facilitates its deprotonation and partially increases the hydration level in the channel, which could trigger subsequent channel opening and ion conduction.

Authors:

^[1];

^[1]

SLAC National Accelerator Lab., Menlo Park, CA (United States). Photon Ultrafast Laser Science and Engineering Inst. (PULSE), and Dept. of Chemistry; Stanford Univ., CA (United States)

Publication Date:: Mon May 13 00:00:00 EDT 2019

Research Org.:: SLAC National Accelerator Lab., Menlo Park, CA (United States)

Sponsoring Org.:: USDOE; National Science Foundation (NSF)

OSTI Identifier:: 1532466

Grant/Contract Number:: AC02-76SF00515; CHE-1740645

Resource Type:: Accepted Manuscript

Journal Name:: Journal of Physical Chemistry Letters

Additional Journal Information:: Journal Volume: 10; Journal Issue: 11; Journal ID: ISSN 1948-7185

Publisher:: American Chemical Society

Country of Publication:: United States

Language:: English

Subject:: 37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY

Citation Formats


                    Liang, Ruibin, Liu, Fang, and Martínez, Todd J. Nonadiabatic Photodynamics of Retinal Protonated Schiff Base in Channelrhodopsin 2.  United States: N. p., 2019. 
Web.  doi:10.1021/acs.jpclett.9b00701.

Copy to clipboard


                    Liang, Ruibin, Liu, Fang, & Martínez, Todd J. Nonadiabatic Photodynamics of Retinal Protonated Schiff Base in Channelrhodopsin 2.  United States.  https://doi.org/10.1021/acs.jpclett.9b00701

Copy to clipboard


                    Liang, Ruibin, Liu, Fang, and Martínez, Todd J. Mon .  
"Nonadiabatic Photodynamics of Retinal Protonated Schiff Base in Channelrhodopsin 2".  United States.  https://doi.org/10.1021/acs.jpclett.9b00701.  https://www.osti.gov/servlets/purl/1532466.

Copy to clipboard


                    
@article{osti_1532466,

  title        = {Nonadiabatic Photodynamics of Retinal Protonated Schiff Base in Channelrhodopsin 2},

  author       = {Liang, Ruibin and Liu, Fang and Martínez, Todd J.},

  abstractNote = {Channelrhodopsin 2 (ChR2) is a light-gated ion channel and an important tool in optogenetics. Photoisomerization of retinal protonated Schiff base (RPSB) in ChR2 triggers channel activation. Despite the importance of ChR2 in optogenetics, the detailed mechanism for photoisomerization and channel activation is still not fully understood. Here, we report on computer simulations to investigate the photoisomerization mechanism and its effect on the activation of ChR2. Nonadiabatic dynamics simulation of ChR2 was carried out using the ab initio multiple spawning (AIMS) method and quantum mechanics/molecular mechanics (QM/MM) with a restricted ensemble Kohn–Sham (REKS) treatment of the QM region. Our results agree well with spectroscopic measurements and reveal that the RPSB isomerization is highly specific around the C13=C14 bond and follows the “aborted bicycle-pedal” mechanism. In addition, RPSB photoisomerization facilitates its deprotonation and partially increases the hydration level in the channel, which could trigger subsequent channel opening and ion conduction.},

  doi          = {10.1021/acs.jpclett.9b00701},

  journal      = {Journal of Physical Chemistry Letters},

  number       = 11,

  volume       = 10,

  place        = {United States},

  year         = {Mon May 13 00:00:00 EDT 2019},

  month        = {Mon May 13 00:00:00 EDT 2019}

}

Copy to clipboard

Journal Article:

Free Publicly Available Full Text

Accepted Manuscript (DOE)

Publisher's Version of Record

https://doi.org/10.1021/acs.jpclett.9b00701

Other availability

Search WorldCat to find libraries that may hold this journal

Citation Metrics:

Cited by: 21 works

Citation information provided by
Web of Science

Save / Share:

Export Metadata

Save to My Library

Similar Records in DOE PAGES and OSTI.GOV collections:

Electrostatic Control of Photoisomerization in Channelrhodopsin 2

Journal Article Liang, Ruibin ; Yu, Jimmy K. ; Meisner, Jan ; ... - Journal of the American Chemical Society

Channelrhodopsin 2 (ChR2) is the most commonly used tool in optogenetics. Because of its faster photocycle compared to wild-type (WT) ChR2, the E123T mutant of ChR2 is a useful optogenetic tool when fast neuronal stimulation is needed. Interestingly, in spite of its faster photocycle, the initial step of the photocycle in E123T (photoisomerization of retinal protonated Schiff base or RPSB) was found experimentally to be much slower than that of WT ChR2. The E123T mutant replaces the negatively charged E123 residue with a neutral T123 residue, perturbing the electric field around the RPSB. Understanding the RPSB photoisomerization mechanism in ChR2more »« less
https://doi.org/10.1021/jacs.1c00058
First-Principles Characterization of the Elusive I Fluorescent State and the Structural Evolution of Retinal Protonated Schiff Base in Bacteriorhodopsin

Journal Article Yu, Jimmy K. ; Liang, Ruibin ; Liu, Fang ; ... - Journal of the American Chemical Society

The conversion of light energy into work is essential to life on earth. Bacteriorhodopsin (bR), a light-activated proton pump in Archae, has served for many years as a model system for the study of this process in photoactive proteins. Upon absorption of a photon, its chromophore, the retinal protonated Schiff base (RPSB), isomerizes from its native all-trans form to a 13-cis form and pumps a proton out of the cell in a process that is coupled to eventual ATP synthesis. Despite numerous time-resolved spectroscopic studies over the years, the details of the photodynamics of bR on the excited state, particularlymore »« less
Cited by 36
https://doi.org/10.1021/jacs.9b08941

Full Text Available
Channelrhodopsin C1C2: Photocycle kinetics and interactions near the central gate

Journal Article VanGordon, Monika R. ; Prignano, Lindsey A. ; Dempski, Robert E. ; ... - Biophysical Journal

Channelrhodopsins (ChR) are light-sensitive cation channels used in optogenetics, a technique that applies light to control cells (e.g., neurons) that have been modified genetically to express those channels. Although mutations are known to affect pore kinetics, little is known about how mutations induce changes at the molecular scale. To address this issue, we first measured channel opening and closing rates of a ChR chimera (C1C2) and selected variants (N297D, N297V, and V125L). Then, we used atomistic simulations to correlate those rates with changes in pore structure, hydration, and chemical interactions among key gating residues of C1C2 in both closed andmore »« less
https://doi.org/10.1016/j.bpj.2021.03.002

Full Text Available
Electrostatic Influence on Photoisomerization in Bacteriorhodopsin and Halorhodopsin

Journal Article Punwong, Chutintorn ; Hannongbua, Supot ; Martínez, Todd J. - Journal of Physical Chemistry. B, Condensed Matter, Materials, Surfaces, Interfaces and Biophysical Chemistry

Bacteriorhodopsin (bR) and halorhodopsin (hR) are mutual membrane proteins that transport ions across the cell membrane in halobacteria. Their ion transport function is triggered by photoactivated isomerization of the retinal protonated Schiff base (RPSB) chromophore. In spite of their similar structures, bR and hR exhibit widely differing RPSB isomerization rates and quantum yields (with bR being both faster and more efficient than hR). Previous simulations of photoisomerization in bR and hR using ab initio multiple spawning (AIMS) with QM/MM have successfully reproduced the experimentally observed ordering of quantum yields and isomerization rates, but the origin of these differences remains elusive.more »« less
Cited by 3
https://doi.org/10.1021/acs.jpcb.9b01837

Full Text Available
Photoisomerization action spectrum of retinal protonated Schiff base in the gas phase

Journal Article Coughlan, N. J. A. ; Catani, K. J. ; Adamson, B. D. ; ... - Journal of Chemical Physics

The photophysical behaviour of the isolated retinal protonated n-butylamine Schiff base (RPSB) is investigated in the gas phase using a combination of ion mobility spectrometry and laser spectroscopy. The RPSB cations are introduced by electrospray ionisation into an ion mobility mass spectrometer where they are exposed to tunable laser radiation in the region of the S{sub 1} ← S{sub 0} transition (420–680 nm range). Four peaks are observed in the arrival time distribution of the RPSB ions. On the basis of predicted collision cross sections with nitrogen gas, the dominant peak is assigned to the all-trans isomer, whereas the subsidiary peaksmore »« less
https://doi.org/10.1063/1.4871883

Similar Records