CAPcAMPmediated

CAP-cAMP mediated regulation refers to the transcriptional activation of certain bacterial operons by the complex formed between the catabolite activator protein (CAP) and cyclic AMP (cAMP). This regulatory mechanism is best described in Escherichia coli and other Gram-negative bacteria, where it links nutrient availability to gene expression, particularly under conditions of low glucose.

Mechanism and mode of action: When glucose levels are low, adenylate cyclase activity increases, raising intracellular cAMP. cAMP binds CAP, inducing a conformational change that enables CAP to dimerize and bind to specific DNA sites near promoters, commonly around the -61.5 region relative to the transcription start site. The CAP-cAMP complex interacts with RNA polymerase, especially the sigma70 holoenzyme, to stabilize promoter binding and enhance transcription initiation. Binding of CAP-cAMP can bend DNA and promote open complex formation, thereby increasing transcription of target operons.

Scope and regulation: CAP-cAMP mediated activation affects a broad set of operons involved in the uptake and metabolism of alternative carbon sources, such as lac, gal, ara, mal, and others. The system functions as a global regulator of catabolite repression, aligning metabolic gene expression with nutrient status. The presence of glucose lowers cAMP, reducing CAP-cAMP binding and downregulating these operons, while glucose scarcity elevates cAMP and upregulates transcription.

Biological significance: This mechanism enables efficient prioritization of preferred carbon sources and integration with other regulatory networks. CAP-cAMP mediated regulation is a foundational example of how small molecule signaling modulates transcription in bacteria.