The tetramerization domain of the tree shrew p53 protein displays unique thermostability despite sharing high sequence identity with the human p53 protein

Nakagawa, Natsumi; Sakaguchi, Shuya; Nomura, Takao; Kamada, Rui; Omichinski, James G.; Sakaguchi, Kazuyasu

doi:10.1016/j.bbrc.2019.10.130

Cited by 3 publications

(3 citation statements)

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“…The peptides corresponding to the human p53 TD (HU-p53TD; residues 324-358 of human p53), the tree shrew p53 tetramerization domain (TS-p53TD; residues 324-358 of tree shrew p53), the guinea pig p53 tetramerization domain (GP-p53TD; residues 321-355 of guinea pig p53), the Chinese hamster p53 tetramerization domain (CH-p53TD; residues 324-358 of Chinese hamster p53), the sheep p53 tetramerization domain (SH-p53TD: residues 313-347 of sheep p53), and the opossum p53 tetramerization domain (OP-p53TD; residues 296-330 of opossum p53) were synthesized as previously described [35]. The peptide sequences are shown in Figure 1.…”

Section: Synthesis Of P53td Peptidesmentioning

confidence: 99%

“…Although the tree shrew is estimated to have diverged from larger primates about 90 million years ago, it is still regarded as a potential model for examining early primate evolution since it represents an early precursor in the evolution pathway leading to apes and humans [32][33][34]. Surprisingly, we recently determined that the TD of the tree shrew p53 protein (TS-p53TD) is dramatically more thermostable than HU-p53TD despite the fact that the two TDs share very a high sequence identity percentage [35]. It was postulated that this difference was important in helping the tree shrew adapt to its unusual diet that includes the daily consumption of large quantities of alcohol, which poses an enhanced risk of DNA damage due to exposure to high levels of the genotoxic agent acetaldehyde.…”

Section: Introductionmentioning

confidence: 99%

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Highly Similar Tetramerization Domains from the p53 Protein of Different Mammalian Species Possess Varying Biophysical, Functional and Structural Properties

Sakaguchi,

Nakagawa,

Wahba

et al. 2023

IJMS

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The p53 protein is a transcriptional regulatory factor and many of its functions require that it forms a tetrameric structure. Although the tetramerization domain of mammalian p53 proteins (p53TD) share significant sequence similarities, it was recently shown that the tree shrew p53TD is considerably more thermostable than the human p53TD. To determine whether other mammalian species display differences in this domain, we used biophysical, functional, and structural studies to compare the properties of the p53TDs from six mammalian model organisms (human, tree shrew, guinea pig, Chinese hamster, sheep, and opossum). The results indicate that the p53TD from the opossum and tree shrew are significantly more stable than the human p53TD, and there is a correlation between the thermostability of the p53TDs and their ability to activate transcription. Structural analysis of the tree shrew and opossum p53TDs indicated that amino acid substitutions within two distinct regions of their p53TDs can dramatically alter hydrophobic packing of the tetramer, and in particular substitutions at positions corresponding to F341 and Q354 of the human p53TD. Together, the results suggest that subtle changes in the sequence of the p53TD can dramatically alter the stability, and potentially lead to important changes in the functional activity, of the p53 protein.

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Section: Synthesis Of P53td Peptidesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Highly Similar Tetramerization Domains from the p53 Protein of Different Mammalian Species Possess Varying Biophysical, Functional and Structural Properties

Sakaguchi,

Nakagawa,

Wahba

et al. 2023

IJMS

Self Cite

View full text Add to dashboard Cite

show abstract

“…p53 plays a role in protecting organisms from genotoxic stresses, in part via enhancing the protein level of Nrf2 [91]. As p53 protective mechanisms include DNA damage induced by acetaldehyde, it is of interest that the p53 protein in tree shrews is considerably more thermostable than human p53, which may lead to superior maintenance of genomic integrity and protection of acetaldehyde-induced DNA damage [92].…”

Section: Metabolic Magicians In Naturementioning

confidence: 99%