Characterization of early and late transition states of the folding pathway of a SH2 domain.

ABSTRACT: Albeit SH2 domains are abundant protein-protein interaction modules with fundamental roles in the regulation of several physiological and molecular pathways in the cell, the available information about the determinants of their thermodynamic stability and folding properties are still very limited. In this work, we provide a quantitative characterization of the folding pathway of the C-terminal SH2 domain of SHP2, conducted through a combination of site-directed mutagenesis and kinetic (un)folding experiments (Φ-value analysis). The energetic profile of the folding reaction of the C-SH2 domain is described by a three-state mechanism characterized by the presence of two transition states and a high-energy intermediate. The production of 29 site-directed variants allowed us to calculate the d

SUBMITTER: Toto A 

PROVIDER: S-EPMC9112803 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature