PUBLICATION
Tracing the Evolution of the p53 Tetramerization Domain
- Authors
- Joerger, A.C., Wilcken, R., Andreeva, A.
- ID
- ZDB-PUB-140905-12
- Date
- 2014
- Source
- Structure (London, England : 1993) 22: 1301-10 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Phylogeny
- Protein Structure, Secondary
- Protein Multimerization
- Zebrafish Proteins/chemistry*
- Zebrafish Proteins/genetics
- Protein Binding
- Protein Structure, Quaternary
- Tumor Suppressor Protein p53/chemistry*
- Tumor Suppressor Protein p53/genetics
- Protein Interaction Domains and Motifs
- Animals
- Molecular Sequence Data
- Evolution, Molecular
- Zebrafish
- Amino Acid Sequence
- Humans
- Crystallography, X-Ray
- Conserved Sequence
- Sequence Analysis, Protein
- PubMed
- 25185827 Full text @ Structure
Citation
Joerger, A.C., Wilcken, R., Andreeva, A. (2014) Tracing the Evolution of the p53 Tetramerization Domain. Structure (London, England : 1993). 22:1301-10.
Abstract
The tetrameric transcription factors p53, p63, and p73 evolved from a common ancestor and play key roles in tumor suppression and development. Surprisingly, p63 and p73 require a second helix in their tetramerization domain for the formation of stable tetramers that is absent in human p53, raising questions about the evolutionary processes leading to diversification. Here we determined the crystal structure of the zebrafish p53 tetramerization domain, which contains a second helix, reminiscent of p63 and p73, combined with p53-like features. Through comprehensive phylogenetic analyses, we systematically traced the evolution of vertebrate p53 family oligomerization domains back to the beginning of multicellular life. We provide evidence that their last common ancestor also had an extended p63/p73-like domain and pinpoint evolutionary events that shaped this domain during vertebrate radiation. Domain compaction and transformation of a structured into a flexible, intrinsically disordered region may have contributed to the expansion of the human p53 interactome.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping