DNA-binding protects p53 from interactions with cofactors involved in transcription-independent functions.

ABSTRACT: Binding-induced conformational changes of a protein at regions distant from the binding site may play crucial roles in protein function and regulation. The p53 tumour suppressor is an example of such an allosterically regulated protein. Little is known, however, about how DNA binding can affect distal sites for transcription factors. Furthermore, the molecular details of how a local perturbation is transmitted through a protein structure are generally elusive and occur on timescales hard to explore by simulations. Thus, we employed state-of-the-art enhanced sampling atomistic simulations to unveil DNA-induced effects on p53 structure and dynamics that modulate the recruitment of cofactors and the impact of phosphorylation at Ser215. We show that DNA interaction promotes a conformational ch

SUBMITTER: Lambrughi M 

PROVIDER: S-EPMC5100575 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature