Glycoprotein interactions in paramyxovirus fusion

描述：(改编自调查人员摘要)：副粘病毒 是成人和儿童的重要呼吸道病原体。少校 副粘病毒感染细胞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。人们可以确定许多相似之处 副粘病毒融合和其他病毒的融合，如流感和 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驻留在 两种不同的表面糖蛋白刺突结构，附着和融合 分别为蛋白质。我们研究的长期目标是 了解副粘病毒糖蛋白与病毒的早期相互作用 细胞表面。附着和融合蛋白，曾经被认为是 独立的，现在被证明参与了特定的交互，即 必须与后者向其聚变活性形式的转换有关。 这项建议的目的是为了了解 这两种蛋白质之间的复合体以及这种复合体如何在 核聚变过程。复杂形成的具体方面将被阐明 包括受体识别的作用，通过末端球状结构域的 附着蛋白，该蛋白必须经历的变化才能参与 与融合蛋白的相互作用以及两种蛋白上的介导位点 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，可能识别新的 控制它们的抗病毒策略。

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.