Papillomavirus E6 Structural Consortium

乳头瘤病毒 E6 结构联盟

• 批准号: 8213684
• 负责人: Scott Brian Vande Pol
• 金额: $ 39.87万
• 依托单位: UNIVERSITY OF VIRGINIA
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-02-01 至 2015-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8213684
• 关键词: Acquired Immunodeficiency Syndrome; Benign Epithelioma; Binding; Biochemical; Biological Process; Bovine Papillomavirus; Cancer Etiology; Cancerous; Cells; Cessation of life; Collaborations; Complex; DNA biosynthesis; Development; Epithelial; Human Papillomavirus; Human papillomavirus 16; In Vitro; Individual; Infection; International; Lead; Length; Leucine; Malignant Neoplasms; Malignant epithelioma; Malignant neoplasm of cervix uteri; Maps; Modeling; Molecular Structure; Mutagenesis; Mutate; Mutation; Normal Cell; Oncogene Proteins; Papillomavirus; Peptides; Pharmaceutical Preparations; Phenotype; Play; Proteins; Role; Solutions; Structural Protein; Structure; Surface; Techniques; Technology; Therapeutic; Virus Replication; Woman; Work; Zinc; base; cellular targeting; design; human UBE3A protein; in vivo; mutant; physical property; protein aminoacid sequence; public health relevance; research study; tumor; viral DNA

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.

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，是一种艾滋病相关恶性肿瘤。乳头状瘤病毒E6癌蛋白在病毒复制中起关键作用，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，由于E6的物理性质使结构研究受挫，几十年来E6蛋白的结构仍然难以阐明。该应用克服了这些困难，并将通过NMR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。 公共卫生关系：乳头瘤病毒导致许多癌症，包括宫颈癌，因为它们产生一种称为E6的蛋白质，有助于使正常细胞变成癌细胞。了解E6的原子结构将有助于我们了解E6是如何工作的，并可能导致针对E6的药物，从而对抗宫颈癌。该应用程序将解决E6的原子结构，并进行实验以显示E6结构如何参与导致癌症。