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  Structural details of light activation of the LOV2-based photoswitch PA-Rac1

Winkler, A., Barends, T., Udvarhelyi, A., Lenherr-Frey, D., Lomb, L., Menzel, A., et al. (2015). Structural details of light activation of the LOV2-based photoswitch PA-Rac1. ACS Chemical Biology, 10(2), 502-509. doi:10.1021/cb500744m.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0026-CEA2-1 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0026-CEA3-0
Genre: Journal Article

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 Creators:
Winkler, Andreas1, Author              
Barends, Thomas1, Author              
Udvarhelyi, Anikó1, Author              
Lenherr-Frey, Daniel1, Author              
Lomb, Lukas1, Author              
Menzel, Andreas, Author
Schlichting, Ilme1, Author              
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1Department of Biomolecular Mechanisms, Max Planck Institute for Medical Research, Max Planck Society, ou_1497700              

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 Abstract: Optical control of cellular processes is an emerging approach for studying biological systems, affording control with high spatial and temporal resolution. Specifically designed artificial photoswitches add an interesting extension to naturally occurring light-regulated functionalities. However, despite a great deal of structural information, the generation of new tools cannot be based fully on rational design yet; in many cases design is limited by our understanding of molecular details of light activation and signal transduction. Our biochemical and biophysical studies on the established optogenetic tool PA-Rac1, the photoactivatable small GTPase Rac1, reveal how unexpected details of the sensor-effector interface, such as metal coordination, significantly affect functionally important structural elements of this photoswitch. Together with solution scattering experiments, our results favor differences in the population of pre-existing conformations as the underlying allosteric activation mechanism of PA-Rac1, rather than the assumed release of the Rac1 domain from the caging photoreceptor domain. These results have implications for the design of new optogenetic tools and highlight the importance of including molecular details of the sensor-effector interface, which is however difficult to assess during the initial design of novel artificial photoswitches

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Language(s): eng - English
 Dates: 2014-10-162014-11-042014-11-172015-02-20
 Publication Status: Published in print
 Pages: 8
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 Table of Contents: -
 Rev. Type: Peer
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Title: ACS Chemical Biology
Source Genre: Journal
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Publ. Info: Washington, D.C. : American Chemical Society
Pages: - Volume / Issue: 10 (2) Sequence Number: - Start / End Page: 502 - 509 Identifier: ISSN: 1554-8929
CoNE: https://pure.mpg.de/cone/journals/resource/1000000000035040