与腺病毒E1A结合的视网膜母细胞瘤蛋白结构揭示了病毒癌蛋白使肿瘤抑制因子失活的分子基础。
Structure of the retinoblastoma protein bound to adenovirus E1A reveals the molecular basis for viral oncoprotein inactivation of a tumor suppressor.
作者信息
Liu Xin, Marmorstein Ronen
机构信息
Program in Gene Expression and Regulation, The Wistar Institute, Philadelphia, Pennsylvania 19104, USA.
出版信息
Genes Dev. 2007 Nov 1;21(21):2711-6. doi: 10.1101/gad.1590607.
Abstract
The adenovirus (Ad) E1A (Ad-E1A) oncoprotein mediates cell transformation, in part, by displacing E2F transcription factors from the retinoblastoma protein (pRb) tumor suppressor. In this study we determined the crystal structure of the pRb pocket domain in complex with conserved region 1 (CR1) of Ad5-E1A. The structure and accompanying biochemical studies reveal that E1A-CR1 binds at the interface of the A and B cyclin folds of the pRb pocket domain, and that both E1A-CR1 and the E2F transactivation domain use similar conserved nonpolar residues to engage overlapping sites on pRb, implicating a novel molecular mechanism for pRb inactivation by a viral oncoprotein.
摘要
腺病毒（Ad）E1A（Ad - E1A）癌蛋白部分通过将视网膜母细胞瘤蛋白（pRb）肿瘤抑制因子中的E2F转录因子置换出来介导细胞转化。在本研究中，我们确定了与Ad5 - E1A保守区域1（CR1）复合的pRb口袋结构域的晶体结构。该结构及相关生化研究表明，E1A - CR1结合于pRb口袋结构域A和B细胞周期蛋白折叠的界面，并且E1A - CR1和E2F反式激活结构域都使用相似的保守非极性残基来占据pRb上的重叠位点，这暗示了病毒癌蛋白使pRb失活的一种新分子机制。
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