The tetramerization domain of the tree shrew p53 protein displays unique thermostability despite sharing high sequence identity with the human p53 protein
Autor: | Natsumi Nakagawa, Rui Kamada, Shuya Sakaguchi, James G. Omichinski, Takao Nomura, Kazuyasu Sakaguchi |
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Rok vydání: | 2019 |
Předmět: |
0301 basic medicine
Models Molecular Normal diet DNA damage Biophysics Mutagenesis (molecular biology technique) Computational biology Biology Biochemistry Domain (software engineering) 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Protein Domains Animals Humans Amino Acid Sequence Molecular Biology Gene Thermostability Methionine Sequence Homology Amino Acid Protein Stability Temperature Tupaiidae Cell Biology Glutamine 030104 developmental biology chemistry 030220 oncology & carcinogenesis Thermodynamics Protein Multimerization Tumor Suppressor Protein p53 |
Zdroj: | Biochemical and biophysical research communications. 521(3) |
ISSN: | 1090-2104 |
Popis: | The p53 protein plays a number of roles in protecting organisms from different genotoxic stresses and this includes DNA damage induced by acetaldehyde, a metabolite of alcohol. Since the common tree shrew ingests high levels of alcohol as part of its normal diet, this suggests that its p53 protein may possess unique properties. Using a combination of biophysical and modeling studies, we demonstrate that the tetramerization domain of the tree shrew p53 protein is considerably more stable than the corresponding domain from humans despite sharing almost 90% sequence identity. Based on modeling and mutagenesis studies, we determine that a glutamine to methionine substitution at position 354 plays a key role in this difference. Given the link between stability of the p53 tetramerization domain and its transcriptional activity, the results suggest that this enhanced stability could lead to important consequences at p53-regulated genes in the tree shrew. |
Databáze: | OpenAIRE |
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