Peter, Emanuel and Dick, Bernhard and Stambolic, Ivan and Baeurle, Stephan A. (2014) Exploring the multiscale signaling behavior of phototropin1 from Chlamydomonas reinhardtii using a full-residue space kinetic Monte Carlo molecular dynamics technique. PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS, 82 (9). pp. 2018-2040. ISSN 0887-3585, 1097-0134
Full text not available from this repository. (Request a copy)Abstract
Devising analysis tools for elucidating the regulatory mechanism of complex enzymes has been a challenging task for many decades. It generally requires the determination of the structural-dynamical information of protein solvent systems far from equilibrium over multiple length and time scales, which is still difficult both theoretically and experimentally. To cope with the problem, we introduce a full-residue space multiscale simulation method based on a combination of the kinetic Monte Carlo and molecular dynamics techniques, in which the rates of the rate-determining processes are evaluated from a biomolecular forcefield on the fly during the simulation run by taking into account the full space of residues. To demonstrate its reliability and efficiency, we explore the light-induced functional behavior of the full-length phototropin1 from Chlamydomonas reinhardtii (Cr-phot1) and its various subdomains. Our results demonstrate that in the dark state the light oxygen voltage-2-J alpha (LOV2-J alpha) photoswitch inhibits the enzymatic activity of the kinase, whereas the LOV1-J alpha photoswitch controls the dimerization with the LOV2 domain. This leads to the repulsion of the LOV1-LOV2 linker out of the interface region between both LOV domains, which results in a positively charged surface suitable for cell-membrane interaction. By contrast, in the light state, we observe that the distance between both LOV domains is increased and the LOV1-LOV2 linker forms a helix-turn-helix (HTH) motif, which enables gene control through nucleotide binding. Finally, we find that the kinase is activated through the disruption of the J alpha-helix from the LOV2 domain, which is followed by a stretching of the activation loop (A-loop) and broadening of the catalytic cleft of the kinase.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | INDUCED STRUCTURAL-CHANGES; DEPENDENT PROTEIN-KINASE; BLUE-LIGHT RECEPTORS; RNA-BINDING MOTIF; J-ALPHA HELIX; ARABIDOPSIS PHOTOTROPIN-1; LOV DOMAINS; CRYSTAL-STRUCTURE; CONFORMATIONAL-CHANGES; ADIANTUM PHYTOCHROME3; multiscale modeling method; combined kinetic Monte Carlo and molecular dynamics technique; signal transduction dynamics; complex signal proteins; phototropin1 from Chlamydomonas reinhardtii; photoenzymes |
| Subjects: | 500 Science > 540 Chemistry & allied sciences |
| Divisions: | Chemistry and Pharmacy > Institut für Physikalische und Theoretische Chemie > Chair of Chemistry III - Physical Chemistry (Molecular Spectroscopy and Photochemistry) > Prof. Dr. Bernhard Dick Chemistry and Pharmacy > Institut für Physikalische und Theoretische Chemie > Chair of Chemistry III - Physical Chemistry (Molecular Spectroscopy and Photochemistry) > PD Dr. Stephan Baeurle |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 29 Aug 2019 11:56 |
| Last Modified: | 29 Aug 2019 11:56 |
| URI: | https://pred.uni-regensburg.de/id/eprint/9693 |
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