Sharma Nitin, Gadhave Kundlik, Kumar Prateek, Giri Rajanish
School of Basic Sciences, Indian Institute of Technology Mandi, Kamand, Himachal Pradesh, 175005, India.
BioX Center, Indian Institute of Technology Mandi, Kamand, Himachal Pradesh, 175005, India.
Curr Res Struct Biol. 2022 Jan 13;4:29-40. doi: 10.1016/j.crstbi.2022.01.001. eCollection 2022.
Transactivation domain of Adenovirus Early region 1A (E1A) oncoprotein is an intrinsically disordered molecular hub protein. It is involved in binding to different domains of human cell transcriptional co-activators such as retinoblastoma (pRb), CREB-binding protein (CBP), and its paralogue p300. The conserved region 1 (TAD) of E1A is known to undergo structural transitions and folds upon interaction with transcriptional adaptor zinc finger 2 (TAZ2). Previous reports on Taz2-E1A studies have suggested the formation of helical conformations of E1A-TAD. However, the folding behavior of the TAD region in isolation has not been studied in detail. Here, we have elucidated the folding behavior of E1A peptide at varied temperatures and solution conditions. Further, we have studied the effects of macromolecular crowding on E1A-TAD peptide. Additionally, we have also predicted the molecular recognition features of E1A using MoRF predictors. The predicted MoRFs are consistent with its structural transitions observed during TAZ2 interactions for transcriptional regulation in literature. Also, as a general rule of MoRFs, E1A undergoes helical transitions in alcohol and osmolyte solution. Finally, we studied the aggregation behavior of E1A, where we observed that the E1A could form amyloid-like aggregates that are cytotoxic to mammalian cells.
腺病毒早期区域1A（E1A）癌蛋白的反式激活结构域是一种内在无序的分子枢纽蛋白。它参与与人细胞转录共激活因子的不同结构域结合，如视网膜母细胞瘤（pRb）、CREB结合蛋白（CBP）及其旁系同源物p300。已知E1A的保守区域1（TAD）在与转录衔接子锌指2（TAZ2）相互作用时会发生结构转变并折叠。先前关于Taz2-E1A研究的报告表明E1A-TAD形成了螺旋构象。然而，TAD区域单独的折叠行为尚未得到详细研究。在这里，我们阐明了E1A肽在不同温度和溶液条件下的折叠行为。此外，我们研究了大分子拥挤对E1A-TAD肽的影响。此外，我们还使用MoRF预测器预测了E1A的分子识别特征。预测的MoRFs与其在文献中TAZ2相互作用进行转录调控期间观察到的结构转变一致。同样，作为MoRFs的一般规律，E1A在酒精和渗透剂溶液中会发生螺旋转变。最后，我们研究了E1A的聚集行为，观察到E1A可以形成对哺乳动物细胞具有细胞毒性的淀粉样聚集体。
