Papillomavirus E6 Structural Consortium

描述(申请人提供)：乳头瘤病毒导致上皮性肿瘤，包括宫颈癌，这是妇女癌症死亡的主要原因，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起关键作用，在宫颈癌的发生发展中起重要作用。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，由于E6的物理性质阻碍了结构研究，因此对E6蛋白的结构的阐明一直难以捉摸。这一应用克服了这些困难，并将通过核磁共振技术解决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联。 与公共卫生相关：乳头瘤病毒导致包括宫颈癌在内的多种癌症，因为它们会产生一种名为E6的蛋白质，有助于将正常细胞转化为癌细胞。了解E6的原子结构将有助于我们了解E6是如何发挥作用的，并可能导致抗E6的药物，从而对抗宫颈癌。这个应用程序将解出E6的原子结构，并进行实验，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.