Regulatory Impact of the C-Terminal Tail on Charge Transfer Pathways in <i>Drosophila</i> 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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MDPI AG
2020-10-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/25/20/4810 |
| _version_ | 1797550465828782080 |
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| author | Martin Richter Benjamin P. Fingerhut |
| author_facet | Martin Richter Benjamin P. Fingerhut |
| author_sort | Martin Richter |
| collection | DOAJ |
| 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 <i>Drosophila</i> 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. |
| first_indexed | 2024-03-10T15:29:41Z |
| format | Article |
| id | doaj.art-8e6186796f27409eba28ecb99bfaa5f6 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T15:29:41Z |
| publishDate | 2020-10-01 |
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| spelling | doaj.art-8e6186796f27409eba28ecb99bfaa5f62023-11-20T17:44:20ZengMDPI AGMolecules1420-30492020-10-012520481010.3390/molecules25204810Regulatory Impact of the C-Terminal Tail on Charge Transfer Pathways in <i>Drosophila</i> CryptochromeMartin Richter0Benjamin P. Fingerhut1Max-Born-Institut für Nichtlineare Optik und Kurzzeitspektroskopie, D-12489 Berlin, GermanyMax-Born-Institut für Nichtlineare Optik und Kurzzeitspektroskopie, D-12489 Berlin, GermanyInterconnected 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 <i>Drosophila</i> 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.https://www.mdpi.com/1420-3049/25/20/4810electron transfercircadian clockcryptochrometryptophan |
| spellingShingle | Martin Richter Benjamin P. Fingerhut Regulatory Impact of the C-Terminal Tail on Charge Transfer Pathways in <i>Drosophila</i> Cryptochrome Molecules electron transfer circadian clock cryptochrome tryptophan |
| title | Regulatory Impact of the C-Terminal Tail on Charge Transfer Pathways in <i>Drosophila</i> Cryptochrome |
| title_full | Regulatory Impact of the C-Terminal Tail on Charge Transfer Pathways in <i>Drosophila</i> Cryptochrome |
| title_fullStr | Regulatory Impact of the C-Terminal Tail on Charge Transfer Pathways in <i>Drosophila</i> Cryptochrome |
| title_full_unstemmed | Regulatory Impact of the C-Terminal Tail on Charge Transfer Pathways in <i>Drosophila</i> Cryptochrome |
| title_short | Regulatory Impact of the C-Terminal Tail on Charge Transfer Pathways in <i>Drosophila</i> Cryptochrome |
| title_sort | regulatory impact of the c terminal tail on charge transfer pathways in i drosophila i cryptochrome |
| topic | electron transfer circadian clock cryptochrome tryptophan |
| url | https://www.mdpi.com/1420-3049/25/20/4810 |
| work_keys_str_mv | AT martinrichter regulatoryimpactofthecterminaltailonchargetransferpathwaysinidrosophilaicryptochrome AT benjaminpfingerhut regulatoryimpactofthecterminaltailonchargetransferpathwaysinidrosophilaicryptochrome |