Integration of light and oxygen signals by archaeal cysteine-less LOV domain

LOV domains are photoreceptor modules found across all three domains of life. They non-covalently bind flavin chromophores and mediate light-induced signaling in diverse biological processes. The canonical photocycle of LOV domains relies on formation of a covalent adduct between the flavin chromophore and the highly conserved cysteine. However, natural cysteine-less LOV domains can still mediate light-induced signaling through flavin photoreduction to the neutral semiquinone (NSQ) radical state. In this work, we investigate a natural cysteine-less LOV domain, designated HsuLOV, from the haloarchaeon Halanaeroarchaeum sulfurireducens. Time-resolved spectroscopy confirms flavin photoreduction and reveals the unprecedented dependence of HsuLOV photoactivity on salinity and oxygen conditions. Specifically, hypersaline anaerobic environments favor reversible flavin photoreduction to the NSQ over photodegradation into lumichrome. This selective photoactivity, along with salinity-modulated chromophore binding and thermal stability, represents HsuLOV haloadaptation to the extreme habitats of its host organism. Moreover, the strong dependence of HsuLOV photoactivity on oxygen availability suggests that cysteine-less LOV domains can function as biosensors that integrate both blue light and oxygen signals.