A novel sugar-stimulated covalent switch in a sugar sensor

The bgl sensory system is composed of a membrane-bound sugar sensor, BglF, and a transcriptional regulator, BglG. The sensor BglF has several enzymati c activities: in its nonstimulated state, it acts as BglG phosphorylase; in the presence of beta -glucoside in the growth medium, it acts as BglG deph osphorylase and as the beta -glucoside phosphotransferase. The same active site on BglF, Cys-24, is responsible for the phosphorylation of both the st imulating sugar and the BglG protein. BglF is composed of three domains, tw o hydrophilic and one hydrophobic. Our previous results suggested that cata lysis of the sugar-stimulated functions depends on specific interactions be tween the B domain, which contains the active site cysteine, and the integr al membrane C domain. We report here that the stimulating sugar triggers th e formation of a disulfide bond between the active site cysteine and anothe r cysteine in the membrane-embedded domain of BglF. Inability of a mutant B glF protein to form the disulfide bridge between the B and C domains correl ates with its inability to catalyze the sugar-stimulated functions. The abi lity of the cysteine residue in BglF to bind covalently either to a phospho ryl group or to another cysteine residue, depending on the protein stimulat ion state, suggests a novel way to control signaling by alternative bond fo rmation.