Binding induced folding in p53-MDM2 complex.

ABSTRACT: The MDM2 N-terminal domain can bind to the transactivation domain of p53 and downregulate its ability to activate transcription. It was found that binding with p53 stabilizes the MDM2 N-terminal domain. Thus the coupling between binding and folding is essential in the normal functional interactions between p53 and MDM2. We have performed explicit-solvent molecular dynamics simulations (MD) for both bound MDM2(N) and apo-MDM2 to study the interdependence of binding and folding in the p53-MDM2 complex. Kinetic analysis of high-temperature MD simulations shows that both bound MDM2(N) and apo-MDM2 unfold via a two-state process. Both kinetics and free energy landscape analyses indicate that bound MDM2 unfolds in the order of p53 unbinding, tertiary unfolding, and finally secondary structure un

SUBMITTER: Chen HF 

PROVIDER: S-EPMC2528056 | biostudies-literature | 2007 Mar

REPOSITORIES: biostudies-literature