STRUCTURE OF THE RETINOBLASTOMA TUMOR-SUPPRESSOR POCKET DOMAIN BOUND TO A PEPTIDE FROM HPV E7

The pocket domain of the retinoblastoma (Rb) tumour suppressor is cent ral to Rb function, and is frequently inactivated by the binding of th e human papilloma virus E7 oncoprotein in cervical cancer. The crystal structure of the Rb pocket bound to a nine-residue E7 peptide contain ing the LxCxE motif, shared by other Rb-binding viral and cellular pro teins, 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 requ ired for the stable folding of the B box. Also highly consented is the extensive A-B interface, suggesting that it may be an additional prot ein-binding site. The A and B boxes each contain the cyclin-fold struc tural motif, with the LxCxE-binding site on the B-box cyclin fold bein g similar to a Cdk2-binding site of cyclin A and to a TBP-binding site of TFIIB.