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Construction of p53 Protein Tetramer Structure
Author(s) -
Carpenter Cassidy
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.712.9
Subject(s) - tetramer , monomer , dna , mutation , chemistry , protein structure , protein quaternary structure , structural biology , suppressor , biophysics , computational biology , crystallography , microbiology and biotechnology , biology , biochemistry , gene , enzyme , organic chemistry , protein subunit , polymer
The p53 protein controls the cell cycle checkpoint responsible for maintaining the integrity of the genome and inactivation of the p53 tumor suppressor is a common development in many different cancers. The monomer structure of p53 supports the hypothesis that DNA binding is critical for the biological activity of p53 and provides a framework for understanding how mutations inactivate it. However, the full tetramer structure, which has not been solved crystallographically in its entirety, is necessary to contextualize the findings from the monomer. Tetramer construction of the p53 protein was carried out using pymol, protein folding, and energy minimization. Additionally, the p53 tetramer interface was characterized by comparing how the tetramer structure interacted with DNA and other monomers contrasted to just the monomer structure. Lastly, high frequency mutations from the literature were mapped in order to identify significant mutations that could disrupt the tetramer formation. The exploration of these mutations on the constructed p53 tetramer provide the ability to understand how mutations to p53 are situated with respect to the tetramerization interfaces.