Interdiction in the Early Folding of the p53 DNA-Binding Domain Leads to Its Amyloid-Like Misfolding.

ABSTRACT: In this article, we investigate two issues: (a) the initial contact formation events along the folding pathway of the DNA-binding domain of the tumor suppressor protein p53 (core p53); and (b) the intermolecular events leading to its conversion into a prion-like form upon incubation with peptide P8(250-257). In the case of (a), the calculations employ the sequential collapse model (SCM) to identify the segments involved in the initial contact formation events that nucleate the folding pathway. The model predicts that there are several possible initial non-local contacts of comparative stability. The most stable of these possible initial contacts involve the protein segments ¹⁵⁹AMAIY¹⁶³ and ²⁵¹ILTII^255, and it is the only native-like contact. Thus

SUBMITTER: Bergasa-Caceres F 

PROVIDER: S-EPMC9370011 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature