Mechanism of signal transduction of the LOV2-Jα photosensor from Avena sativa

• Published in: Nature communications 2010-11, Vol.1 (8), p.122-122, Article 122
• Main Authors: Baeurle, Stephan A, Peter, Emanuel, Dick, Bernhard
• Format: Article
• Language: English
• Subjects: 631/449/2675; 631/449/2686; 631/57/2272; 639/638/439/944; Humanities and Social Sciences; multidisciplinary; Science; Science (multidisciplinary)
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms1121

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. Fusion proteins containing blue-light-activated domains have been used as molecular switches to investigate cell signalling, but molecular understanding of the transduction pathway is lacking. Here, MD simulations are used to elucidate the transduction mechanism in a light oxygen voltage2-Ja photosensor.