DNA Binding Domain of El and Its Interaction With DNA

描述(申请人提供)：牛乳头瘤病毒是一种 一大类密切相关的病毒中的一员，这些病毒会在 他们的主人。生殖道感染由人类病毒引起的 该组织是病毒之间为数不多的牢固建立的联系之一 感染与宫颈癌的发生发展。尽管发展到 恶性肿瘤是一种低频率的事件，这是由于 感染后，这种疾病会影响到大量的个体。BPV已经发挥了作用 作为这一组的原型，特别是关于病毒DNA复制。这个 EL蛋白属于多功能病毒蛋白家族，其主要功能是 功能与病毒DNA复制有关。这些蛋白质与起源结合在一起。 也有其他与DNA复制相关的活动 包括DNA扭曲和DNA解旋酶活性。此外，这些 蛋白质与细胞复制蛋白相互作用，如DNA pola和 RPA。因此，这一组蛋白质密切参与启动 DNA复制。 该提案的目标是提供高分辨率的结构 有关BPV EL启动子蛋白及其DNA结合活性的信息。 从这项研究中获得的信息将与两个领域相关：第一 是提供对涉及到的生化事件的总体洞察 病毒DNA复制。这反过来又可以为发展提供基础。 临床干预策略。其次，病毒的DNA复制 机械本身就是抗病毒治疗的明显目标， 详细信息，如病毒蛋白的高分辨率结构 复制所需的资源将极大地方便开发和测试 抗病毒药物。

DESCRIPTION (Provided by the applicant): Bovine Papillomavirus (BPV) is a member of a large family of closely related viruses that give rise to warts in their hosts. Infection of the genital tract by the human viruses from this group represents one of the few firmly established links between viral infection and the development of cervical cancer. Although the progression to malignancy represents a low frequency event, due to the high frequency of infection, this disease affects a large number of individuals. BPV has served as a prototype for this group especially regarding viral DNA replication. The El protein belongs to a family of multifunctional viral proteins whose main function is related to viral DNA replication. These proteins bind to the origin of DNA replication, and also have other activities related to DNA replication including a DNA distortion and a DNA helicase activity. Furthermore, these proteins interact with cellular replication proteins such as DNA pol alpha and RPA. Thus, this group of proteins are intimately involved with initiation of DNA replication. The objectives of this proposal are to provide high resolution structural information about the BPV El initiator protein and its DNA binding activity. The information gained from this study will be relevant in two areas: The first is to provide general insight into the biochemical events that are involved in viral DNA replication. This, in turn, can provide a basis for the development of clinical intervention strategies. Secondly, the viral DNA replication machinery itself represents an obvious target for antiviral therapy and detailed information such as high resolution structures of viral proteins required for replication will greatly facilitate the development and testing of antiviral agents.