The extremely thermophilic bacterium Thermus thermophilus HB8, which belongs to the phylum DeinococcusThermus, has an open reading frame encoding a protein belonging to the cyclic AMP (cAMP) receptor protein (CRP) family present in many bacteria. The protein named T. thermophilus CRP is highly homologous to the CRP family proteins from the phyla Firmicutes, Actinobacteria, and Cyanobacteria, and it forms a homodimer and interacts with cAMP. CRP mRNA and intracellular cAMP were detected in this strain, which did not drastically fluctuate during cultivation in a rich medium. The expression of several genes was altered upon disruption of the T. thermophilus CRP gene. We found six CRP-cAMP-dependent promoters in in vitro transcription assays involving DNA fragments containing the upstream regions of the genes exhibiting de- Cyclic AMP (cAMP) receptor proteins (CRPs) are global transcriptional regulators broadly distributed in bacteria (30,72). The cellular roles of such CRP family proteins are diverse and include carbohydrate metabolism (3, 30), development of competence for transformation (8), modulation of virulence gene expression and pathogenesis (10,11,55,57,65), resuscitation (50), and germination and morphological development (13,49).Escherichia coli CRP controls the activity of over 100 genes and has been the most extensively studied so far (30, 72). This CRP was first named the catabolite gene-activating protein, since it induces the transcription of a number of genes in response to carbon source limitation (16,73). In the absence of a carbon source such as glucose, the intracellular cAMP level increases, resulting in the formation of a CRP-cAMP complex, which binds to specific DNA sequences at target promoters. The CRP-cAMP regulatory complex is also involved in the regulation of genes that are not directly related to catabolism (3). In addition, the complex acts as a negative regulator of transcription at cya gene promoter cyaP2, gal operon promoter galP2, crp gene promoter crpP, and deo operon promoter deoP2 (3). E. coli CRP is a dimer of two identical subunits, each 209 residues in length, and contains a helix-turn-helix DNA-binding motif in its C-terminal domain (40). Each subunit can bind one molecule of allosteric effector cAMP. This CRP undergoes a conformational change upon cAMP binding (21,66,67), and the CRP-cAMP complex interacts with a 22-bp DNA site exhibiting twofold symmetry, with the consensus sequence 5Ј-AAATGTGATCTAGATCACATTT-3Ј (15). Biochemical and genetic analyses have revealed that this CRP interacts with the C-terminal domain of the RNA polymerase (RNAP) ␣ subunit (␣CTD) (5,6,24,35,43,44,58). This interaction is thought to facilitate RNAP binding to the promoter, which leads to the formation of an open complex and induction of transcription initiation. Crystallographic studies on E. coli CRP have been performed to determine the structure of CRP-cAMP and the mechanisms underlying the interactions among CRP-cAMP, DNA, and RNAP ␣CTD (30, 34).CRP homologs have been found not only in othe...