Structure of the retinoblastoma tumour-suppressor pocket domain bound to a peptide from HPV E7

• Published in: Nature (London) 1998-02, Vol.391 (6670), p.859-865
• Main Authors: Pavletich, Nikola P, Lee, Jie-Oh, Russo, Alicia A
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Binding Sites; Biological and medical sciences; Cancer; Conserved Sequence; Crystallography, X-Ray; Cyclins - chemistry; Fundamental and applied biological sciences. Psychology; Human papillomavirus; Humanities and Social Sciences; Humans; Interactions. Associations; Intermolecular phenomena; Medical research; Models, Molecular; Molecular biophysics; Molecular Sequence Data; multidisciplinary; Neoplasms - metabolism; Oncogene Proteins, Viral - chemistry; Oncogene Proteins, Viral - metabolism; Papillomavirus E7 Proteins; Phosphorylation; Protein Binding; Protein Conformation; Proteins; Recombinant Proteins - chemistry; Retinoblastoma Protein - chemistry; Retinoblastoma Protein - metabolism; Science; Science (multidisciplinary)
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/36038

The pocket domain of the retinoblastoma (Rb) tumour suppressor is central to Rb function, and is frequently inactivated by the binding of the human papilloma virus E7 oncoprotein in cervical cancer. The crystal structure of the Rb pocket bound to a nine-residue E7 peptide containing the LxCxE motif, shared by other Rb-binding viral and cellular proteins, shows that the LxCxE peptide binds a highly conserved groove on the B-box portion of the pocket; the A-box portion appears to be required for the stable folding of the B box. Also highly conserved is the extensive A–B interface, suggesting that it may be an additional protein-binding site. The A and B boxes each contain the cyclin-fold structural motif, with the LxCxE-binding site on the B-box cyclin fold being similar to a Cdk2-binding site of cyclin A and to a TBP-binding site of TFIIB.