Phosphorylation of KLHL3 at serine 433 impairs its interaction with the acidic motif of WNK4: a molecular dynamics study.

ABSTRACT: Interaction between the acidic motif (AM) of protein kinase WNK4 and the Kelch domain of KLHL3 are involved in the pathogenesis of pseudohypoaldosteronism type II, a hereditary form of hypertension. This interaction is disrupted by some disease-causing mutations in either WNK4 or KLHL3, or by angiotensin II- and insulin-induced phosphorylation of KLHL3 at serine 433, which is also a site frequently mutated in patients. However, the mechanism by which this phosphorylation disrupts the interaction is unclear. In this study, we approached this problem using molecular dynamics simulation with structural, dynamical and energetic analyses. Results from independent simulations indicate that when S433 was phosphorylated, the electrostatic potential became more negative in the AM binding site of KL

SUBMITTER: Wang L 

PROVIDER: S-EPMC5275730 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature