Solution structure of a conserved C-terminal domain of p73 with structural homology to the SAM domain.
p73 and p63 are two recently cloned genes with homology to the tumor suppressor p53, whose protein product is a key transcriptional regulator of genes involved in cell cycle arrest and apoptosis. While all three proteins share conserved transcriptional activation, DNA-binding and oligomerization domains, p73 and p63 have an additional conserved C-terminal region. We have determined the three-dimensional solution structure of this conserved C-terminal domain of human p73. The structure reveals a small five-helix bundle with striking similarity to the SAM (sterile alpha motif) domains of two ephrin receptor tyrosine kinases. The SAM domain is a putative protein-protein interaction domain found in a variety of cytoplasmic signaling proteins and has been shown to form both homo- and hetero-oligomers. However, the SAM-like C-terminal domains of p73 and p63 are monomeric and do not interact with one another, suggesting that this domain may interact with additional, as yet uncharacterized proteins in a signaling and/or regulatory role.
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Ontario Cancer Institute and Department of Medical Biophysics, University of Toronto, 610 University Avenue, Toronto, Ontario, Canada M5G 2M9.
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Arrowsmith
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D000595:Amino Acid Sequence; D017124:Conserved Sequence; D004268:DNA-Binding Proteins / Q000737:chemistry*; D005326:Fetal Proteins / Q000737:chemistry; D016147:Genes, Tumor Suppressor; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D009687:Nuclear Proteins / Q000737:chemistry*; D017510:Protein Folding; D020794:Receptor Protein-Tyrosine Kinases / Q000737:chemistry; D036122:Receptor, EphA4; D036183:Receptor, EphB2; D017386:Sequence Homology, Amino Acid; D012996:Solutions; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins
D004268:DNA-Binding Proteins; D005326:Fetal Proteins; D009687:Nuclear Proteins; D012996:Solutions; C000606460:TP73 protein, human; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins; D020794:Receptor Protein-Tyrosine Kinases; D036122:Receptor, EphA4; D036183:Receptor, EphB2