Papillomavirus E6 Structural Consortium

描述（由申请人提供）：乳头瘤病毒引起上皮肿瘤，包括宫颈癌，宫颈癌是女性癌症死亡的主要原因，也是一种与艾滋病相关的恶性肿瘤。乳头瘤病毒 E6 癌蛋白在病毒复制中发挥着关键作用，并且在宫颈癌的发展中至关重要。 E6 的分子结构对于治疗策略的设计至关重要。不幸的是，几十年来，E6 蛋白的结构的阐明一直难以捉摸，因为 E6 的物理特性阻碍了结构研究。本申请克服了这些困难，将通过NMR技术解析E6的溶液结构。 E6在原子水平上的结构特征将与其多种生物学功能相关。 公共健康相关性：乳头瘤病毒会导致多种癌症，包括宫颈癌，因为它们会产生一种名为 E6 的蛋白质，帮助正常细胞转变为癌细胞。了解 E6 的原子结构将有助于我们了解 E6 的工作原理，并可能开发出针对 E6 的药物，从而对抗宫颈癌。该应用程序将解析E6的原子结构，并进行实验来展示E6结构如何参与致癌。

DESCRIPTION (provided by applicant): Papillomaviruses cause epithelial tumors including cervical cancer, which is a leading cause of cancer deaths in women and is an AIDS-associated malignancy. The papillomavirus E6 oncoprotein plays a critical role in virus replication and is essential in the development of cervical cancer. A molecular structure of E6 is critical for the design of therapeutic strategies. Unfortunately, elucidating the structure of the E6 protein has remained elusive for decades because the physical properties of E6 have frustrated structural studies. This application has overcome these difficulties and will solve the solution structure of E6 by NMR techniques. The structural features of E6 at the atomic level will be correlated to its multiple biological functions. PUBLIC HEALTH RELEVANCE: Papillomaviruses cause numerous cancers, including cervical cancer, because they make a protein called E6 that helps make normal cells into cancerous cells. Understanding the atomic structure of E6 will aid our understanding of how E6 works, and could lead to drugs that act against E6 and thereby against cervical cancer. This application will solve the atomic structure of E6 and perform experiments to show how the E6 structure participates in causing cancer.