Revisiting the mechanism of activation of cyclic AMP receptor protein (CRP) by cAMP in Escherichia coli: lessons from a subunit-crosslinked form of CRP.

Cyclic AMP receptor protein (CRP), the global transcription regulator in prokaryotes, is active only as a cAMP-CRP complex. Binding of cAMP changes the conformation of CRP, transforming it from a transcriptionally 'inactive' to an 'active' molecule. These conformers are also characterized by distinct biochemical properties including the ability to form an S-S crosslink between the C178 residues of its two monomeric subunits. We studied a CRP variant (CRP(cl)), in which the subunits are crosslinked. We demonstrate that CRP(cl) can activate transcription even in the absence of cAMP. Implications of these results for the crystallographically-determined structure of cAMP-CRP are discussed.