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#CAP protein

3 public questions tagged with this topic.

Catabolite repression is caused by

Catabolite repression establishes hierarchical sugar utilization favoring glucose over lactose for optimal growth efficiency. Elevated glucose transport through phosphotransferase system converts EIIA-Glc to dephosphorylated form that directly inhibits LacY permease activity and reduces adenylate cyclase activation, substantially decreasing intracellular cyclic AMP concentration. Without sufficient cAMP, catabolite activator protein CAP remains as inactive dimer unable to bind its target DNA site centered at -61.5 relative to lac promoter transcription start. RNA polymerase holoenzyme affinity for promoter falls, initiation frequency declines approximately fiftyfold, and lactose metabolism remains silenced even when lactose present, ensuring preferential glucose consumption.

Ref: NCBI PMC Quantitative approaches to lac bistability – glucose lowers cAMP, CAP fails to bind upstream site, catabolite repression.

CAP becomes active when bound to

Catabolite activator protein exists in equilibrium between inactive and active conformations controlled by small molecule ligand binding allosterically. Each protomer of the homodimer contains N-terminal cyclic-nucleotide-binding domain that specifically accommodates cyclic AMP in anti conformation. cAMP binding triggers hinge repositioning and ordering of C-terminal helix-turn-helix DNA recognition motif able to bind consensus TGTGA-N6-TCACA half sites with high affinity. Resulting CRP-cAMP-DNA ternary complex bends DNA and activates transcription initiation. ATP and GTP do not serve as allosteric effectors for this protein, glucose actually lowers cAMP indirectly via PTS-mediated regulation of adenylate cyclase enzymatic activity controlling synthesis.

Ref: NCBI Biochemistry - CAP becomes active when bound to cAMP allosteric activation; Alberts Chapter 7 catabolite repression

Positive regulation of lac operon involves

Lac operon integrates two environmental signals via negative and positive inputs ensuring efficient carbon utilization hierarchy. Catabolite activation provides positive regulation: when glucose scarce, adenylate cyclase raises cyclic AMP concentration, enabling CRP-CAP dimer formation. CAP, also known as catabolite activator protein, binds upstream site at -61.5, introduces 90-degree DNA bending, and contacts alpha-carboxy-terminal domain of RNA polymerase, stabilizing binding and promoting isomerization to open complex and enhancing transcription roughly fifty-fold beyond basal derepressed level. LacI repressor causes negative inhibition blocking polymerase, IPTG acts as derepressor mimicking inducer allolactose, and beta-galactosidase is structural enzyme downstream of regulatory control mechanisms.

Ref: Alberts Fig 7-39 CAP-cAMP positive regulator; NCBI - CAP binds DNA to activate lac transcription in low glucose