A proposal for a dipole-generated BLUF domain mechanism

Abstract

The resting and signaling structures of the blue-light sensing using flavin (BLUF) photoreceptor domains are still controversially debated due to differences in the molecular models obtained by crystal and NMR structures. Photocycles for the given preferred structural framework have been established, but a unifying picture combining experiment and theory remains elusive. We summarize present work on the AppA BLUF domain from both experiment and theory. We focus on IR and UV/vis spectra, and to what extent theory was able to reproduce experimental data and predict the structural changes upon formation of the signaling state. We find that the experimental observables can be theoretically reproduced employing any structural model, as long as the orientation of the signaling essential Gln63 and its tautomer state are a choice of the modeler. We also observe that few approaches are comparative, e.g., by considering all structures in the same context. Based on recent experimental findings and a few basic calculations, we suggest the possibility for a BLUF activation mechanism that only relies on electron transfer and its effect on the local electrostatics, not requiring an associated proton transfer. In this regard, we investigate the impact of dispersion correction on the interaction energies arising from weakly bound amino acids.

Structural insight into photoactivation of an adenylate cyclase from a photosynthetic cyanobacterium

“…The simplest proposed sensing mechanism is a rotamer shift of the glutamine, so that after stimulation, this side chain donates a hydrogen bond to the C4=O carbonyl and accepts one from the tyrosine, whereas in the dark state, the glutamine donates to the tyrosine (11,13,14). In BlrP1, these changes are accompanied by movement of a nearby methionine on the β5-strand of the BLUF domain, and both "Met in " and "Met out " arrangements have been described (15).…”

Light-induced chromophore and protein responses and mechanical signal transduction of BLUF proteins

“…The photoreaction of flavin is, in many cases, observed as the light-induced redox reactions with the aromatic amino acids involving the transfers of proton and electron in picosecond timescale (Kao et al 2008 ; Mataga et al 2000 ; Tanaka et al 2007 ). In BLUF proteins as well, the low fluorescence quantum yields of the FAD chromophore (Tyagi et al 2008 ; Zirak et al 2007 ; Zirak et al 2005 , 2006 ) is indicative of a photochemical reaction, which lies behind the hydrogen-bond structural change in the active site (Conrad et al 2014 ; Kennis and Mathes 2013 ; Mathes and Gotze 2015 ).…”

“…These photoreceptors bind various types of chromophores that absorb light energy of different wavelengths and thereby convert the absorbed energy into conformational changes by various mechanisms. Blue light–using flavin (BLUF) proteins, which are found in many bacteria and certain algae, are photoreceptors that contain a flavin chromophore that absorbs blue light (Gomelsky and Klug 2002 ; Masuda 2013 ; Conrad et al 2014 ; Mathes and Gotze 2015 ). The chromophore-binding domain (~15 kDa), denoted as the BLUF domain, is present in single- and multi-domain proteins, and it transmits the light-induced signal to downstream protein modules via intermolecular or intramolecular interactions.…”

Role of active site conformational changes in photocycle activation of the AppA BLUF photoreceptor

“…Despite numerous experimental and computational studies (8,(13)(14)(15)(16)(17), the exact nature of the signaling state and the mechanism of long-range signaling in BLUF proteins are not well understood. The active site conformation in even the dark-adapted state is still under debate because of discrepancies in the orientations of the key active site Trp, Met, and Gln residues among different experimental crystal and solution structures of BLUF domains (18)(19)(20)(21)(22)(23)(24)(25)(26).…”