title: Mechanism of signal transduction of the LOV2-Jα photosensor from Avena sativa.
abstract: Fusion proteins containing blue-light-activable protein domains possess great potential as molecular switches in cell signalling. This has recently been impressively demonstrated by connecting the light oxygen voltage LOV2-Jα-protein domain of A. sativa (AsLOV2-Jα) with the Rac1-GTPase, responsible for regulating the morphology and motility of metazoan cells. However, a target-oriented development of fusion proteins in conjunction with this photosensor is still very challenging, because a detailed understanding of its signal transduction pathway on a molecular level is still lacking. Here, we show through molecular dynamics simulation that, after formation of the cysteinyl-flavin mononucleotide (FMN) adduct, the signalling pathway begins with a rotational reorientation of the residue glutamine 1029 adjacent to the FMN chromophore, transmitting stress through the Iβ strand towards the LOV2-Jα interface. This then results in the breakage of two H-bonds, namely, glutamic acid 1034-Gln995 and aspartic acid (Asp) 1056-Gln1013, at opposite sides of the interface between the Jα helix and the LOV2 domain, ultimately leading to a disruption of Jα helix from the LOV2 core.
authors.affiliation: Department of Chemistry and Pharmacy, Institute of Physical and Theoretical Chemistry, University of Regensburg, Regensburg, Bavaria D-93053, Germany.
authors.forename: Emanuel
authors.initials: E
authors.lastname: Peter
authors.forename: Bernhard
authors.initials: B
authors.lastname: Dick
authors.forename: Stephan A
authors.initials: SA
authors.lastname: Baeurle