Role of non-native electrostatic interactions in the coupled folding and binding of PUMA with Mcl-1.

ABSTRACT: PUMA, which belongs to the BH3-only protein family, is an intrinsically disordered protein (IDP). It binds to its cellular partner Mcl-1 through its BH3 motif, which folds upon binding into an α helix. We have applied a structure-based coarse-grained model, with an explicit Debye-Hückel charge model, to probe the importance of electrostatic interactions both in the early and the later stages of this model coupled folding and binding process. This model was carefully calibrated with the experimental data on helical content and affinity, and shown to be consistent with previously published experimental data on binding rate changes with respect to ionic strength. We find that intramolecular electrostatic interactions influence the unbound states of PUMA only marginally. Our results further su

SUBMITTER: Chu WT 

PROVIDER: S-EPMC5400261 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature