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J Mol Biol. 2012 May 25;419(1-2):61-74. doi: 10.1016/j.jmb.2012.02.037. Epub 2012 Mar 7.

The amino-terminal helix modulates light-activated conformational changes in AsLOV2.

Author information

1
Department of Biochemistry and Molecular Biology, The University of Chicago, Chicago, IL 60637, USA.

Abstract

The mechanism of light-triggered conformational change and signaling in light-oxygen-voltage (LOV) domains remains elusive in spite of extensive investigation and their use in optogenetic studies. The LOV2 domain of Avenasativa phototropin 1 (AsLOV2), a member of the Per-Arnt-Sim (PAS) family, contains a flavin mononucleotide chromophore that forms a covalent bond with a cysteine upon illumination. This event leads to the release of the carboxy-terminal Jα helix, the biological output signal. Using mutational analysis, circular dichroism, and NMR, we find that the largely ignored amino-terminal helix is a control element in AsLOV2's light-activated conformational change. We further identify a direct amino-to-carboxy-terminal "input-output" signaling pathway. These findings provide a framework to rationalize the LOV domain architecture, as well as the signaling mechanisms in both isolated and tandem arrangements of PAS domains. This knowledge can be applied in engineering LOV-based photoswitches, opening up new design strategies and improving existing ones.

PMID:
22406525
PMCID:
PMC3338903
DOI:
10.1016/j.jmb.2012.02.037
[Indexed for MEDLINE]
Free PMC Article

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