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Regulatory Impact of the C-Terminal Tail on Charge Transfer Pathways in Drosophila Cryptochrome

Interconnected transcriptional and translational feedback loops are at the core of the molecular mechanism of the circadian clock. Such feedback loops are synchronized to external light entrainment by the blue light photoreceptor cryptochrome (CRY) that undergoes conformational changes upon light ab...

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Autores principales: Richter, Martin, Fingerhut, Benjamin P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7587983/
https://www.ncbi.nlm.nih.gov/pubmed/33086760
http://dx.doi.org/10.3390/molecules25204810
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author Richter, Martin
Fingerhut, Benjamin P.
author_facet Richter, Martin
Fingerhut, Benjamin P.
author_sort Richter, Martin
collection PubMed
description Interconnected transcriptional and translational feedback loops are at the core of the molecular mechanism of the circadian clock. Such feedback loops are synchronized to external light entrainment by the blue light photoreceptor cryptochrome (CRY) that undergoes conformational changes upon light absorption by an unknown photoexcitation mechanism. Light-induced charge transfer (CT) reactions in Drosophila CRY (dCRY) are investigated by state-of-the-art simulations that reveal a complex, multi-redox site nature of CT dynamics on the microscopic level. The simulations consider redox-active chromophores of the tryptophan triad (Trp triad) and further account for pathways mediated by W314 and W422 residues proximate to the C-terminal tail (CTT), thus avoiding a pre-bias to specific W-mediated CT pathways. The conducted dissipative quantum dynamics simulations employ microscopically derived model Hamiltonians and display complex and ultrafast CT dynamics on the picosecond timescale, subtly balanced by the electrostatic environment of dCRY. In silicio point mutations provide a microscopic basis for rationalizing particular CT directionality and demonstrate the degree of electrostatic control realized by a discrete set of charged amino acid residues. The predicted participation of CT states in proximity to the CTT relates the directionality of CT reactions to the spatial vicinity of a linear interaction motif. The results stress the importance of CTT directional charge transfer in addition to charge transfer via the Trp triad and call for the use of full-length CRY models including the interactions of photolyase homology region (PHR) and CTT domains.
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spelling pubmed-75879832020-10-29 Regulatory Impact of the C-Terminal Tail on Charge Transfer Pathways in Drosophila Cryptochrome Richter, Martin Fingerhut, Benjamin P. Molecules Article Interconnected transcriptional and translational feedback loops are at the core of the molecular mechanism of the circadian clock. Such feedback loops are synchronized to external light entrainment by the blue light photoreceptor cryptochrome (CRY) that undergoes conformational changes upon light absorption by an unknown photoexcitation mechanism. Light-induced charge transfer (CT) reactions in Drosophila CRY (dCRY) are investigated by state-of-the-art simulations that reveal a complex, multi-redox site nature of CT dynamics on the microscopic level. The simulations consider redox-active chromophores of the tryptophan triad (Trp triad) and further account for pathways mediated by W314 and W422 residues proximate to the C-terminal tail (CTT), thus avoiding a pre-bias to specific W-mediated CT pathways. The conducted dissipative quantum dynamics simulations employ microscopically derived model Hamiltonians and display complex and ultrafast CT dynamics on the picosecond timescale, subtly balanced by the electrostatic environment of dCRY. In silicio point mutations provide a microscopic basis for rationalizing particular CT directionality and demonstrate the degree of electrostatic control realized by a discrete set of charged amino acid residues. The predicted participation of CT states in proximity to the CTT relates the directionality of CT reactions to the spatial vicinity of a linear interaction motif. The results stress the importance of CTT directional charge transfer in addition to charge transfer via the Trp triad and call for the use of full-length CRY models including the interactions of photolyase homology region (PHR) and CTT domains. MDPI 2020-10-19 /pmc/articles/PMC7587983/ /pubmed/33086760 http://dx.doi.org/10.3390/molecules25204810 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Richter, Martin
Fingerhut, Benjamin P.
Regulatory Impact of the C-Terminal Tail on Charge Transfer Pathways in Drosophila Cryptochrome
title Regulatory Impact of the C-Terminal Tail on Charge Transfer Pathways in Drosophila Cryptochrome
title_full Regulatory Impact of the C-Terminal Tail on Charge Transfer Pathways in Drosophila Cryptochrome
title_fullStr Regulatory Impact of the C-Terminal Tail on Charge Transfer Pathways in Drosophila Cryptochrome
title_full_unstemmed Regulatory Impact of the C-Terminal Tail on Charge Transfer Pathways in Drosophila Cryptochrome
title_short Regulatory Impact of the C-Terminal Tail on Charge Transfer Pathways in Drosophila Cryptochrome
title_sort regulatory impact of the c-terminal tail on charge transfer pathways in drosophila cryptochrome
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7587983/
https://www.ncbi.nlm.nih.gov/pubmed/33086760
http://dx.doi.org/10.3390/molecules25204810
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