Glycoprotein interactions in paramyxovirus fusion

副粘病毒融合中的糖蛋白相互作用

• 批准号: 6319140
• 负责人: RONALD M IORIO
• 金额: $ 34.99万
• 依托单位: UNIV OF MASSACHUSETTS MED SCH WORCESTER
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-04-01 至 2006-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6319140
• 关键词: Paramyxovirus; glycoproteins; intermolecular interaction; membrane proteins; tissue /cell culture; virus infection mechanism; virus protein

DESCRIPTION: (Adapted from the Investigator's abstract): The paramyxoviruses are important respiratory pathogens of both adults and children. The major cytopathic effect in paramyxovirus-infected cells is the formation of multi-nucleate syncytia. This is mediated by membrane fusion, induced by the two viral surface glycoproteins. One can identify many similarities between paramyxovirus fusion and those of other viruses, such as the influenza and human immunodeficiency viruses. However, unlike the other viruses, the paramyxovirus receptor recognition and fusion-promoting activities reside on two different surface glycoprotein spike structures, the attachment and fusion proteins, respectively. The long-term goal of our research has been to understand the early interactions of the paramyxovirus glycoproteins with the cell surface. The attachment and fusion proteins, once thought to be independent, have now been shown to take part in a specific interaction that is obligatorily linked to the conversion of the latter to its fusion-active form. The objective of this proposal is to understand the mechanism of formation of the complex between the two proteins and how this complex functions in the fusion process. Specific aspects of complex formation that will be elucidated include the role of receptor recognition by the terminal globular domain of the attachment protein, the changes this protein must undergo to take part in the interaction with the fusion protein and the sites on both proteins that mediate the interaction. This information will help elucidate how these important pathogens gain entry into, and spread between, cells, possibly identifying new anti-viral strategies for their control.

描述：（改编自研究者的摘要）：副粘病毒 是成人和儿童的重要呼吸道病原体。主要 副粘病毒感染细胞中的细胞病变效应是形成 多核合胞体。这是由膜融合介导的，由 两种病毒表面糖蛋白。人们可以发现两者之间有许多相似之处 副粘病毒融合体与其他病毒（例如流感病毒和流感病毒）的融合体 人类免疫缺陷病毒。然而，与其他病毒不同的是， 副粘病毒受体识别和融合促进活性位于 两种不同的表面糖蛋白刺突结构，附着和融合 分别是蛋白质。我们研究的长期目标是 了解副粘病毒糖蛋白与 细胞表面。附着蛋白和融合蛋白曾经被认为是 独立的，现在已被证明参与特定的相互作用 必然与后者转化为其融合活性形式有关。 该提案的目的是了解形成机制 两种蛋白质之间的复合物以及该复合物如何在 融合过程。将阐明复合物形成的具体方面 包括末端球状结构域受体识别的作用 附着蛋白，该蛋白质必须经历的变化才能参与 与融合蛋白以及两种蛋白上介导的位点的相互作用 的互动。这些信息将有助于阐明这些重要的 病原体进入细胞并在细胞之间传播，可能识别出新的 控制其的抗病毒策略。