Amplification of signaling via cellular allosteric relay and protein disorder

摘要

Historical perspectives and the underlying mechanisms of allostery have been recently reviewed (1-4), increasingly highlighting conformation selection and population shift (5). A classical example is transcription factor (TF) catabolite activator protein (CAP) activation by cAMP in response to extracellular stimuli (6). cAMP-CAP-DNA complex was the first TF with 3D structure (7), and it was postulated that cAMP binding causes structural rearrangements allowing CAP to bind DNA (6, 8). Twenty-eight years later, NMR structures have confirmed the allosteric transition paradigm; as reported in this issue of PNAS, Popovych et al. (9) found that without cAMP binding, the CAP apo form loses 3 helical turns and the DNA binding domain rotates, shifting from its DNA binding-ready state. Consistent with theoretical expectation, some mutations shifted the ensemble toward a DNA-compatible active state even without cAMP binding (9).