Paramyxovirus Entry

副粘病毒进入

• 批准号: 6400855
• 负责人: Trudy G. Morrison
• 金额: $ 31.47万
• 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: 2001-09-30 至 2002-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6400855
• 关键词: Newcastle disease virus; conformation; glycoproteins; membrane fusion; point mutation; protein protein interaction; protein sequence; protein structure function; tissue /cell culture; virus infection mechanism; virus protein

DESCRIPTION (provided by applicant): The goal of our studies is to understand the molecular mechanisms of paramyxovirus membrane fusion using Newcastle disease virus as a prototype. As in most paramyxovirus systems, membrane fusion requires both HN and F proteins. Our studies have focused on two questions, how the F protein mediates membrane fusion and the role of RN protein in that process. Our mutational analysis of the F protein has shown that two heptad repeat domains, HR1 and HR2, are important in the fusion activity of the protein. We have shown that peptides with sequences from these domains interact but likely only upon activation of fusion. We have also found that sequences from the HN protein will interact with a specific domain within the F protein. Furthermore, we have made a point mutation within another F protein heptad repeat domain, HR3, which eliminated the absolute requirement for RN protein in fusion. To address the questions raised by these findings we propose four specific aims: 1) To determine limits of HN protein and F protein interacting domains. 2) To characterize the interactions of peptides and peptide analogues from the HR1, HR2, and RN sequences in order to clarify mechanisms involved in fusion inhibition by F mutants, to identify residues important for conformational shifts, and to identify residues important in RN-F protein interactions. 3) To define the nature of conformational shifts in the glycoproteins using peptides, peptide analogues, as well as peptide specific antisera. 4). To explore the role attachment in initiation of fusion.

描述（由申请人提供）：我们研究的目标是了解 使用纽卡斯尔研究副粘病毒膜融合的分子机制 疾病病毒作为原型。与大多数副粘病毒系统一样，膜融合 需要 HN 和 F 蛋白。我们的研究主要集中在两个问题上： F 蛋白介导膜融合以及 RN 蛋白在其中的作用 过程。我们对 F 蛋白的突变分析表明，两个七肽 重复结构域 HR1 和 HR2 在融合活性中非常重要 蛋白质。我们已经证明具有这些结构域序列的肽会相互作用 但很可能只有在融合激活时才会发生。我们还发现序列 来自 HN 蛋白的分子将与 F 蛋白内的特定结构域相互作用。 此外，我们在另一个 F 蛋白七肽中进行了点突变 重复结构域 HR3，消除了对 RN 蛋白的绝对需求 融合。为了解决这些发现提出的问题，我们提出了四个建议 具体目标：1）确定HN蛋白和F蛋白相互作用的限度 域。 2) 表征肽和肽类似物的相互作用 从 HR1、HR2 和 RN 序列中，以阐明参与的机制 F突变体的融合抑制，以确定重要的残基 构象转变，并鉴定 RN-F 蛋白中重要的残基 互动。 3）定义构象转变的性质 使用肽、肽类似物以及肽特异性的糖蛋白 抗血清。 4）。探索融合启动中的角色依恋。