7PC6

DNA-binding domain of a p53 homolog from the hydrothermal vent annelid Alvinella pompejana

Summary for 7PC6

• Entry DOI: 10.2210/pdb7pc6/pdb
• Descriptor: DNA-binding domain, ZINC ION, 1,2-ETHANEDIOL, ... (4 entities in total)
• Functional Keywords: p53 family, transcription factor, protein evolution, hydrothermal vents, extremophile, protein stability, transcription
• Biological source: Alvinella pompejana
• Total number of polymer chains: 8
• Total formula weight: 186102.18

Authors

Balourdas, D.-I.,Knapp, S.,Soussi, T.,Joerger, A.C.,Structural Genomics Consortium (SGC) (deposition date: 2021-08-03, release date: 2022-03-23, Last modification date: 2024-11-20)

Primary citation

Zhang, Q.,Balourdas, D.I.,Baron, B.,Senitzki, A.,Haran, T.E.,Wiman, K.G.,Soussi, T.,Joerger, A.C.
Evolutionary history of the p53 family DNA-binding domain: insights from an Alvinella pompejana homolog.
Cell Death Dis, 13:214-214, 2022

PubMed Abstract: The extremophile Alvinella pompejana, an annelid worm living on the edge of hydrothermal vents in the Pacific Ocean, is an excellent model system for studying factors that govern protein stability. Low intrinsic stability is a crucial factor for the susceptibility of the transcription factor p53 to inactivating mutations in human cancer. Understanding its molecular basis may facilitate the design of novel therapeutic strategies targeting mutant p53. By analyzing expressed sequence tag (EST) data, we discovered a p53 family gene in A. pompejana. Protein crystallography and biophysical studies showed that it has a p53/p63-like DNA-binding domain (DBD) that is more thermostable than all vertebrate p53 DBDs tested so far, but not as stable as that of human p63. We also identified features associated with its increased thermostability. In addition, the A. pompejana homolog shares DNA-binding properties with human p53 family DBDs, despite its evolutionary distance, consistent with a potential role in maintaining genome integrity. Through extensive structural and phylogenetic analyses, we could further trace key evolutionary events that shaped the structure, stability, and function of the p53 family DBD over time, leading to a potent but vulnerable tumor suppressor in humans.

PubMed: 35256607
DOI: 10.1038/s41419-022-04653-8

Experimental method

X-RAY DIFFRACTION (1.92 Å)