Model for Z-form adoption by Zα. First, Zα binds to a right-handed B- or A-form helix non-specifically (step 1). Next, the duplex transiently melts, which may be promoted through Zα binding (step 2). The dynamics of these steps occur on a relatively faster time scale (on the micro- to millisecond time regime). From here, the ribose sugar pucker and nucleosides have to rearrange into a high-energy, Z-like state (which occurs slowly taking seconds to hours, step 3). Then, Zα cooperatively binds to and stabilizes the Z-conformation (which occurs fast once a Z-like state is adopted, step 4)).