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Research Article Volume 7 Issue 1
p53 tumor suppressor protein mutants R175H, G245S, R249S and R282W: structural prediction and analysis of full length proteins
Kelly M Thayer, Lisa Je
Department of Chemistry, Vassar College, USA
Received: February 02, 2018 | Published: February 28, 2018
Citation: Thayer KM, Je L. p53 tumor suppressor protein mutants R175H, G245S, R249S and R282W: structural prediction and analysis of full length proteins. MOJ Proteomics Bioinform. 2018;7(1): 00217. DOI: 10.15406/mojpb.2018.07.00217
Abstract
The tumor suppressor protein p53 prevents cancerous formation through its role as a transcription factor to suppress cell division, activate DNA repair, or, if cells are beyond salvageable, induce apoptosis. Proper function of p53 requires the chelation of a zinc ion to stabilize the DNA binding domain that interfaces the DNA. When p53 acquires a mutation, one mechanism by which p53 function can be comprised is through disruption of zinc update, leading to a destabilized protein structure unable to correctly discriminate binding sites and/or aggregation. Therefore, an understanding of the structural perturbations caused by mutant structures is important as a first step towards developing therapeutics to stabilize the protein in an effort to restore native function to the p53 protein.
The structure of p53 has been solved with x-ray crystallography for the DNA binding domain and cryo-electron microscopy for a complex. However, structural coordinates for the full 393 amino acid sequences of p53 and its mutants free in solution are lacking. This is due to the highly flexible nature of the N- and C-terminal regions, compositely comprising roughly half of the protein. Furthermore, capabilities to generate a structural model to investigate any desired mutation carries merit for facilitation research endeavors. In a recent study, we reported the full-length p53 structure based on the Phyre2 protein folding server. In this study we generate the structure of the full-length p53 protein containing each of four point mutations associated with structural instability and loss of an essential zinc cofactor.
Keywords: protein data base, IDP, intrinsically disordered protein; IDR, intrinsically disordered region; MD, Molecular dynamics, NTD, N-terminal domain, also amino terminal domain, CTD, C-terminal domain, also carboxy terminal domain
©2018 Thayer, et al. This is an open access article distributed under the terms of the, which permits unrestricted use, distribution, and build upon your work non-commercially.