DNA Binding Domain of El and Its Interaction With DNA

描述（由申请方提供）：牛乳头瘤病毒（BPV）是一种 一个密切相关的病毒大家族的成员，引起皮肤疣， 他们的主人。生殖道感染的人类病毒从这个 这一组代表了病毒之间少数牢固建立的联系之一， 感染和宫颈癌的发展。虽然进展到 恶性肿瘤代表低频率事件，由于高频率的 感染，这种疾病影响了大量的人。BPV服务于 作为这一组的原型，特别是关于病毒DNA复制。的 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。这些蛋白质结合到 以及其他与DNA复制有关的活动 包括DNA畸变和DNA解旋酶活性。而且这些 蛋白质与细胞复制蛋白如DNA聚合酶α相互作用， RPA。因此，这组蛋白质密切参与启动 DNA复制。 本提案的目的是提供高分辨率的结构 关于BPV El起始蛋白及其DNA结合活性的信息。 从这项研究中获得的信息将在两个方面相关： 是为了提供对生物化学事件的一般了解， 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。第二，病毒DNA复制 机械本身代表了抗病毒治疗的明显目标， 病毒蛋白质的高分辨率结构等详细信息 将大大促进开发和测试 抗病毒剂。

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.