Lee J O, Russo A A, Pavletich N P
Howard Hughes Medical Institute, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
Nature. 1998 Feb 26;391(6670):859-65. 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.
视网膜母细胞瘤（Rb）肿瘤抑制因子的口袋结构域对Rb功能至关重要，并且在宫颈癌中常因人类乳头瘤病毒E7癌蛋白的结合而失活。Rb口袋与包含LxCxE基序的九肽E7肽结合的晶体结构，其他与Rb结合的病毒和细胞蛋白也具有该基序，结果表明LxCxE肽结合口袋B盒部分上一个高度保守的凹槽；A盒部分似乎是B盒稳定折叠所必需的。同样高度保守的是广泛的A - B界面，这表明它可能是一个额外的蛋白质结合位点。A盒和B盒均包含细胞周期蛋白折叠结构基序，B盒细胞周期蛋白折叠上的LxCxE结合位点类似于细胞周期蛋白A的Cdk2结合位点以及TFIIB的TBP结合位点。
