Solution structure of a conserved C-terminal domain of p73 with structural homology to the SAM domain

Abstract

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.