Vorobiev_2009_Proteins_74_526

Human retinoblastoma binding protein 9 (RBBP9) is one of the HCPIN proteins targeted by NESG. RBBP9 was initially identified as the product of a new gene, Bog (for B5T over-expressed gene), in several transformed rat liver epithelial cell lines resistant to the growth-inhibitory effect of TGF-1 as well as in primary human liver tumours. RBBP9 contains the retinoblastoma (Rb) binding motif LxCxE in its sequence, and was shown to interact with Rb by yeast two-hybrid and co-immunoprecipitation experiments 2. Mutation of the Leu residue in this motif to Gln blocked the binding to Rb. RBBP9 can displace E2F1 from E2F1-Rb complexes, and over-expression of RBBP9 overcomes TGF-1 induced growth arrest and results in transformation of rat liver epithelial cells leading to hepatoblastoma-like tumours in nude mice 2. RBBP9 may also play a role in cellular responses to chronic low dose radiation. A close homolog of RBBP9, sharing 93% amino acid sequence identity and also known as RBBP10, interacts with a protein with sua5-yciO-yrdC domains. Amino acid sequence analysis suggests that RBBP9 belongs to the DUF1234 superfamily and may have the alpha/beta hydrolase fold. The closest sequence homolog with structural information is that of the YdeN protein from Bacillus subtilis, which shares only 26% sequence identity with RBBP9. We report here the crystal structure of the 21 kD human RBBP9 at 1.72 A resolution.