Document Detail


Regulatory mechanism of the light-activable allosteric switch LOV-TAP for the control of DNA binding: A computer simulation study.
MedLine Citation:
PMID:  23042418     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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 multi-protein 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 LOV-TAP, in which the light-oxygen-voltage-2-Jα photoswitch of phototropin1 from Avena Sativa (AsLOV2-Jα) has been ligated to the tryptophan-repressor protein (TrpR) 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 LOV-TAP at the molecular level, using the noninvasive molecular dynamics simulation technique. More specifically, we find that Cys450-FMN-adduct formation in the AsLOV2-Jα-binding pocket after photoexcitation induces the cleavage of the peripheral Jα-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 inter-linking the AsLOV2-Jα- and TrpR-domains, ultimately enabling the condensation of LOV-TAP onto the DNA surface. By contrast, in the dark state the AsLOV2-Jα 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 LOV-TAP from the DNA. Proteins 2012. © 2012 Wiley Periodicals, Inc.
Authors:
Emanuel Peter; Bernhard Dick; Stephan A Baeurle
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-10-8
Journal Detail:
Title:  Proteins     Volume:  -     ISSN:  1097-0134     ISO Abbreviation:  Proteins     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-8     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8700181     Medline TA:  Proteins     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012 Wiley Periodicals, Inc.
Affiliation:
Department of Chemistry and Pharmacy, Institute of Physical and Theoretical Chemistry, University of Regensburg, D-93040 Regensburg, Germany.
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