Unfolding, aggregation, and amyloid formation by the tetramerization domain from mutant p53 associated with lung cancer.

ABSTRACT: The p53 tumor suppressor is a tetrameric transcriptional enhancer, and its activity is compromised by mutations that cause amino acid substitutions in its tetramerization domain. Here we analyze the biochemical and biophysical properties of peptides corresponding to amino acids 319-358 of wild-type human p53, which includes the tetramerization domain, and that of a cancer-derived mutant with valine substituted for glycine 334. Unlike the wild-type peptide, the G334V peptide forms amyloid fibrils by a two-step process under physiological conditions of temperature and pH. Nevertheless, the G334V peptide is capable of forming heterooligomers with a wild-type peptide. Computational modeling of the G334V peptide structure suggests that substitution of valine for glycine 334 causes a local disto

SUBMITTER: Higashimoto Y 

PROVIDER: S-EPMC2536691 | biostudies-literature | 2006 Feb

REPOSITORIES: biostudies-literature