The transition state for coupled folding and binding of a disordered DNA binding domain resembles the unbound state.

ABSTRACT: The basic zippers (bZIPs) are one of two large eukaryotic families of transcription factors whose DNA binding domains are disordered in isolation but fold into stable α-helices upon target DNA binding. Here, we systematically disrupt pre-existing helical propensity within the DNA binding region of the homodimeric bZIP domain of cAMP-response element binding protein (CREB) using Ala-Gly scanning and examine the impact on target binding kinetics. We find that the secondary structure of the transition state strongly resembles that of the unbound state. The residue closest to the dimerization domain is largely folded within both unbound and transition states; dimerization apparently propagates additional helical propensity into the basic region. The results are consistent with electrostaticall

SUBMITTER: Kuravsky M 

PROVIDER: S-EPMC11514473 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature