title: Allosteric regulation of the cAMP receptor protein.
abstract: The cyclic AMP receptor protein (CRP) of Escherichia coli is a dimer made up of identical subunits. Each CRP subunit contains a cyclic nucleotide binding pocket and the CRP dimer exhibits negative cooperativity in binding cAMP. In solutions containing cAMP, CRP undergoes sequential conformation changes from the inactive apo-form through the active CRP:(cAMP)(1) complex to the less active CRP:(cAMP)(2) complex depending on the cAMP concentration. Apo-CRP binds DNA with low affinity and no apparent sequence specificity. The CRP:(cAMP)(1) complex exhibits high affinity, sequence-specific DNA binding and interacts with RNA polymerase, whether free in solution or complexed with DNA. The results of genetic, biochemical and biophysical studies have helped to uncover many of the details of cAMP-mediated allosteric control over CRP conformation and activity as a transcription factor. These studies indicate that cAMP binding produces only small, but significant, changes in CRP structure; changes that include subunit realignment and concerted motion of the secondary structure elements within the C-terminal DNA binding domain of each subunit. These adjustments promote CRP surface-patch interaction with RNA polymerase and protrusion of the F-helix to promote CRP site-specific interaction with DNA. Interactions between CRP and RNA polymerase at CRP-dependent promoters produce active ternary transcription complexes.
authors.affiliation: Department of Chemistry and Biochemistry, Texas Tech University, Lubbock, TX 79409, USA. u4jgh@ttacs.ttu.edu
authors.forename: J G
authors.initials: JG
authors.lastname: Harman
mesh_terms: D000494:Allosteric Regulation; D001665:Binding Sites; D000242:Cyclic AMP / Q000737:chemistry*; D012321:DNA-Directed RNA Polymerases / Q000737:chemistry; D004926:Escherichia coli; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D009154:Mutation; D011487:Protein Conformation; D011953:Receptors, Cyclic AMP / Q000737:chemistry* / Q000235:genetics
chemical_list: D011953:Receptors, Cyclic AMP; D000242:Cyclic AMP; D012321:DNA-Directed RNA Polymerases