Structural Basis of Mutation-Dependent p53 Tetramerization Deficiency.

ABSTRACT: The formation of a tetrameric assembly is essential for the ability of the tumor suppressor protein p53 to act as a transcription factor. Such a quaternary conformation is driven by a specific tetramerization domain, separated from the central DNA-binding domain by a flexible linker. Despite the distance, functional crosstalk between the two domains has been reported. This phenomenon can explain the pathogenicity of some inherited or somatically acquired mutations in the tetramerization domain, including the widespread R337H missense mutation present in the population in south Brazil. In this work, we combined computational predictions through extended all-atom molecular dynamics simulations with functional assays in a genetically defined yeast-based model system to reveal structural featu

SUBMITTER: Rigoli M 

PROVIDER: S-EPMC9316806 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature