Solution structure of the Sox2 DNA-binding domain reveals conformational selection in DNA binding.

ABSTRACT: The transcription factor Sox2 is a master regulator of cell pluripotency. While structural studies have provided insights into its DNA-bound conformation, the mechanisms governing its free-state conformational dynamics and DNA recognition remain elusive. Based on solution NMR spectroscopy and supported by molecular dynamics simulations, we here report the solution structure of the Sox2 DNA-binding domain (DBD), revealing that its helical core is well-structured and arranged as in its DNA-bound state. The folded, free protein coexists in dynamic equilibrium with partially unfolded states, which are quenched upon specific DNA binding. We show that the electrostatic environment significantly influences the Sox2-DBD stability, with high ionic strength stabilizing the protein. NMR titration exp

SUBMITTER: Orsetti A 

PROVIDER: S-EPMC12585912 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature