PRD - A PROTEIN DOMAIN INVOLVED IN PTS-DEPENDENT INDUCTION AND CARBONCATABOLITE REPRESSION OF CATABOLIC OPERONS IN BACTERIA

Several operon-specific transcriptional regulators, including antiterm inators and activators, contain a duplicated conserved domain, the PTS regulation domain (PRD). These duplicated domains modify the activity of the transcriptional regulators both positively and negatively. PRD -containing regulators are very common in Gram-positive bacteria. In c ontrast, antiterminators controlling beta-glucoside utilization are th e only functionally characterized members of this family from Gram-neg ative bacteria. PRD-containing regulators are controlled by PTS-depend ent phosphorylation with different consequences: (i) In the absence of inducer, the phosphorylated EIIB component of the sugar permease dona tes its phosphate to a PRD, thereby inactivating the regulator. In the presence of the substrate, the regulator is dephosphorylated, and the phosphate is transferred to the sugar, resulting in induction of the operon. (ii) In Gram-positive bacteria, a novel mechanism of carbon ca tabolite repression mediated by PRD-containing regulators has been dem onstrated. In the absence of PTS substrates, the HPr protein is phosph orylated by enzyme I at His-15. This form of HPr can, in turn, phospho rylate PRD-containing regulators and stimulate their activity. In the presence of rapidly metabolizable carbon sources, ATP-dependent phosph orylation of HPr at Ser-46 by HPr kinase inhibits phosphorylation by e nzyme I, and PRD-containing regulators cannot, therefore, be stimulate d and are inactive. All regulators of this family contain two copies o f PRD, which are functionally specialized in either induction or catab olite repression.