Structural Studies of Paramyxovirus fusion proteins

描述（由申请人提供）：副粘病毒感染人类和动物宿主，并负责引起重大人类疾病，以及具有重大经济后果的动物感染。大多数副粘病毒进入细胞需要附着蛋白HN、H或G（取决于病毒）和融合糖蛋白(F)。本课题将研究HN蛋白的结构和功能，以更好地了解其柄区如何控制F蛋白活化的特异性，从而触发膜融合。我们将确定为什么HN蛋白的一个子集需要蛋白水解激活步骤来实现受体结合、受体破坏和融合促进活性。该提案还将侧重于F糖蛋白的研究，以深入了解副粘病毒家族中预融合构象的潜在结构差异，并更好地了解中和抗体如何参与和抑制F蛋白的功能。该研究将为这些副粘病毒进入糖蛋白如何介导感染提供重要的新见解，并可能为开发抗病毒治疗方法提供新的途径。

DESCRIPTION (provided by applicant): The Paramyxoviruses infect human and animal hosts and are responsible for causing major human illnesses, as well as animal infections of significant economic consequence. The entry into cells of most Paramyxoviruses requires an attachment protein, HN, H or G, depending on the virus, and a fusion (F) glycoprotein. In this proposal will study the structure and function of the HN protein to better understand how its stalk region controls the specificity of F protein activation, thereby triggering membrane fusion. We will determine why a subset of HN proteins require a proteolytic activation step to enable receptor binding, receptor destroying and fusion promoting activities. This proposal will also focus on the study of the F glycoproteins, to gain insight into potential structural differences in the prefusion conformations across the paramyxovirus family and to better understand how neutralizing antibodies engage and inhibit F protein functions. The proposed research will provide significant new insights into how these paramyxovirus entry glycoproteins mediate infection and potentially provide new avenues for the development of antiviral therapeutics.