Structural, Dynamical, and Energetical Consequences of Rett Syndrome Mutation R133C in MeCP2.

ABSTRACT: Rett Syndrome (RTT) is a progressive neurodevelopmental disease affecting females. RTT is caused by mutations in the MECP2 gene and various amino acid substitutions have been identified clinically in different domains of the multifunctional MeCP2 protein encoded by this gene. The R133C variant in the methylated-CpG-binding domain (MBD) of MeCP2 is the second most common disease-causing mutation in the MBD. Comparative molecular dynamics simulations of R133C mutant and wild-type MBD have been performed to understand the impact of the mutation on structure, dynamics, and interactions of the protein and subsequently understand the disease mechanism. Two salt bridges within the protein and two critical hydrogen bonds between the protein and DNA are lost upon the R133C mutation. The mutation wa

SUBMITTER: Kucukkal TG 

PROVIDER: S-EPMC4431600 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature