EL222 is a light-sensitive protein from the marine bacterium Erythrobacter litoralis that regulates gene expression in response to blue light. This regulation occurs through structural changes triggered by the activation of a small molecule inside the protein, called flavin mononucleotide (FMN).
To better understand how EL222 functions, the NMR group of the IBS, and researchers from the Institute of Biotechnology of the Czech Academy of Sciences, investigated chemical and structural changes of EL222 under blue light exposure by a combination of X-ray crystallography, nuclear magnetic resonance (NMR) and optical spectroscopy, as well as molecular simulations.They reveal that EL222 transitions through two distinct light-activated states, each linked to specific chemical changes in FMN. While EL222 is mostly monomeric in the dark, light exposure promotes dimer formation, which enhances its ability to bind to DNA. Surprisingly, all EL222 forms can associate with DNA, but shifting the equilibrium towards stable complexes requires blue light exposure.
This study proposes a new activation model, where light-induced chemical modifications in FMN shift EL222 towards an open conformation that facilitates self-association and DNA binding, ultimately controlling gene expression. It also paves the way for optimizing EL222-based optogenetic tools by adjusting light intensity to fine-tune gene expression levels more precisely.
Light-dependent flavin redox and adduct states control the conformation and DNA-binding activity of the transcription factor EL222. Chaudhari AS, Favier A, Tehrani ZA, Kovaľ T, Andersson I, Schneider B, Dohnálek J, Černý J, Brutscher B, Fuertes G. Nucleic Acids Res. 2025 ; 53(6):gkaf215. doi : 10.1093/nar/gkaf215.
Contact : Bernhard Brutscher (IBS/Biomolecular NMR Spectroscopy Group)