Fig. 5. The folding-before-binding model for DNA recognition by intrinsically disordered CytR^N as a regulatory switch.

(A) CytR^N is intrinsically disordered in its native state, and the molecular recognition event leading to the DNA-bound functional form involves a CS-based folding-before-binding mechanism. (B) A model for how the disorder-to-order transition in CytR^N turns on the regulatory switch into the functional state and primes it for DNA binding, while the large entropy of the disordered state favors the dissociation of the complex and subsequent unfolding of the folded conformation, resetting the switch into the off mode. Molecular dynamics traces of CytR^N are schematic representations and do not correspond to actual data.