Zusammenfassung
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-J alpha-protein domain of A. sativa (AsLOV2-J alpha) with the Rac1-GTPase, responsible for regulating the morphology and motility of metazoan cells. However, a target-oriented ...
Zusammenfassung
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-J alpha-protein domain of A. sativa (AsLOV2-J alpha) 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 I beta strand towards the LOV2-J alpha 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 J alpha helix and the LOV2 domain, ultimately leading to a disruption of J alpha helix from the LOV2 core.
Altmetric