Fig. 7: Signal transduction in light-oxygen-voltage (LOV) receptors lacking the conserved glutamine, exemplified for the A. sativa phototropin 1 LOV2 domain.

a Lewis formulae show the flavin- nucleotide chromophore and surrounding residues of the glutamine-deficient leucine variant in the dark-adapted (left) and light-adapted states (right). As revealed by X-ray crystallography (see Fig. 5), qualitatively similar structural responses to light-induced N5 protonation (see Fig. 1) are observed in both the absence of the conserved glutamine Q513 and in its presence (see Suppl. Fig. 15). Without the glutamine, water molecules might transiently enter the chromophore-binding pocket, thereby stand-in for the glutamine, and relay the signal as changes in hydrogen bonding to the Iβ and Aβ strands of the central β pleated sheet (involving residues N414 and 513). Notably, signals are thus also propagated to the LOV C terminus (D515) which is frequently engaged in signal transduction, and often exhibits a conserved DIT motif⁶. b The observation that LOV receptors can transduce signals without either or both of their strongly conserved cysteine and glutamine residues suggests a potential origin from redox-active flavoproteins¹⁴. LOV signal transduction in a primordial LOV ancestor lacking the Cys and Gln residues would have relied on flavin photoreduction to the NSQ radical and on water mediation. Both the Cys and Gln residues would be secondary acquisitions that minimize side reactions (Cys); enhance the fidelity of signal transduction (Cys and Gln); bathochromically shift the action spectrum (Gln); accelerate the dark recovery and thereby benefit temporal resolution (Cys and Gln); and render the signaling state less susceptible to the cellular environment (Cys). Note that we have no evidence in which sequential order the Gln and Cys residues may have been acquired.