Dokumentenart: | Artikel | ||||
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Titel eines Journals oder einer Zeitschrift: | Proteins: Structure, Function, and Bioinformatics | ||||
Verlag: | WILEY-BLACKWELL | ||||
Ort der Veröffentlichung: | HOBOKEN | ||||
Band: | 81 | ||||
Nummer des Zeitschriftenheftes oder des Kapitels: | 3 | ||||
Seitenbereich: | S. 394-405 | ||||
Datum: | 2013 | ||||
Institutionen: | Chemie und Pharmazie > Institut für Physikalische und Theoretische Chemie Chemie und Pharmazie > Institut für Physikalische und Theoretische Chemie > Chair of Chemistry III - Physical Chemistry (Molecular Spectroscopy and Photochemistry) Chemie und Pharmazie > Institut für Physikalische und Theoretische Chemie > Chair of Chemistry III - Physical Chemistry (Molecular Spectroscopy and Photochemistry) > PD Dr. Stephan Baeurle | ||||
Identifikationsnummer: |
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Stichwörter / Keywords: | J-ALPHA HELIX; SIGNAL-TRANSDUCTION; GENE-EXPRESSION; CHLAMYDOMONAS-REINHARDTII; ADIANTUM PHYTOCHROME3; STRUCTURAL BASIS; AVENA-SATIVA; DOMAIN; PATHWAY; PROTEIN; computer simulation of fusion proteins; LOV-based photoenzymes; light-regulated gene transcription; early signal transduction pathway; protein engineering | ||||
Dewey-Dezimal-Klassifikation: | 500 Naturwissenschaften und Mathematik > 540 Chemie | ||||
Status: | Veröffentlicht | ||||
Begutachtet: | Ja, diese Version wurde begutachtet | ||||
An der Universität Regensburg entstanden: | Ja | ||||
Dokumenten-ID: | 62805 |
Zusammenfassung
The spatio-temporal control of gene expression is fundamental to elucidate cell proliferation and deregulation phenomena in living systems. Novel approaches based on light-sensitive multiprotein complexes have recently been devised, showing promising perspectives for the noninvasive and reversible modulation of the DNA-transcriptional activity in vivo. This has lately been demonstrated in a ...
Zusammenfassung
The spatio-temporal control of gene expression is fundamental to elucidate cell proliferation and deregulation phenomena in living systems. Novel approaches based on light-sensitive multiprotein complexes have recently been devised, showing promising perspectives for the noninvasive and reversible modulation of the DNA-transcriptional activity in vivo. This has lately been demonstrated in a striking way through the generation of the artificial protein construct light-oxygen-voltage (LOV)tryptophan-activated protein (TAP), in which the LOV-2-Ja photoswitch of phototropin1 from Avena sativa (AsLOV2-Ja) has been ligated to the tryptophan-repressor (TrpR) protein from Escherichia coli. Although tremendous progress has been achieved on the generation of such protein constructs, a detailed understanding of their functioning as opto-genetical tools is still in its infancy. Here, we elucidate the early stages of the light-induced regulatory mechanism of LOVTAP at the molecular level, using the noninvasive molecular dynamics simulation technique. More specifically, we find that Cys450-FMN-adduct formation in the AsLOV2-Ja-binding pocket after photoexcitation induces the cleavage of the peripheral Ja-helix from the LOV core, causing a change of its polarity and electrostatic attraction of the photoswitch onto the DNA surface. This goes along with the flexibilization through unfolding of a hairpin-like helix-loop-helix region interlinking the AsLOV2-Ja- and TrpR-domains, ultimately enabling the condensation of LOVTAP onto the DNA surface. By contrast, in the dark state the AsLOV2-Ja photoswitch remains inactive and exerts a repulsive electrostatic force on the DNA surface. This leads to a distortion of the hairpin region, which finally relieves its tension by causing the disruption of LOVTAP from the DNA. Proteins 2013. (C) 2012 Wiley Periodicals, Inc.
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