Long-range modulation of chain motions within the intrinsically disordered transactivation domain of tumor suppressor p53.

ABSTRACT: The tumor suppressor p53 is a hub protein with a multitude of binding partners, many of which target its intrinsically disordered N-terminal domain, p53-TAD. Partners, such as the N-terminal domain of MDM2, induce formation of local structure and leave the remainder of the domain apparently disordered. We investigated segmental chain motions in p53-TAD using fluorescence quenching of an extrinsic label by tryptophan in combination with fluorescence correlation spectroscopy (PET-FCS). We studied the loop closure kinetics of four consecutive segments within p53-TAD and their response to protein binding and phosphorylation. The kinetics was multiexponential, showing that the conformational ensemble of the domain deviates from random coil, in agreement with previous findings from NMR spectrosc

SUBMITTER: Lum JK 

PROVIDER: S-EPMC3265989 | biostudies-literature | 2012 Jan

REPOSITORIES: biostudies-literature