INFLUENZA HEMAGGLUTININ AS A MODEL ACYLPROTEIN

脂肪酸部分与蛋白质的共价结合是 许多病毒和细胞广泛的翻译后修饰 蛋白质。脂肪酸被认为对人体健康具有重要作用 受体组装，蛋白酶保护，生长调节， 形态发生、膜锚定和膜融合。然而， 酰化的最基本方面和脂肪的作用 酸在蛋白质结构和功能中的作用尚不清楚 明白了。特性最好的膜糖蛋白之一 也是一种酰基蛋白质；流感病毒血凝素(HA)。 最近的研究表明，脂肪酸对HA在 膜融合过程--病毒的关键事件 感染性及其在真核生物中持续存在的过程 细胞。我建议对克隆的HA进行定点突变 合成肽用于基因和细胞游离酰基转移酶检测 确定基本结构要求的衬底 蛋白质脂肪酸的酰化及其功能表征 脂肪酸在膜融合和萌发中的作用。这些 实验旨在验证这样一种假设，即脂肪酸 可显著影响结构或生物 分子的性质。取得的成果将会增加。 我们对这种重要的人类病原体的理解 改进我们对广泛的翻译后修饰的看法 从病毒学背景到许多细胞蛋白质。

The covalent attachment of fatty acid moieties to proteins is a widespread postranslational modification of many viral and cell proteins. Fatty acids have been suggested to be important in receptor assembly, protease protection, growth regulation, morphogenesis, membrane anchorage and membrane fusion. However, the most fundamental aspects of acylation and the role fatty acids play in protein structure and function are not yet understood. One of the best characterized membrane glycoproteins is also an acylprotein; the influenza virus hemagglutinin (HA). Recent studies have implicated fatty acid on the HA in the process of membrane fusion, an event crucial for virus infectivity and a process occurring continuously in eukaryotic cells. I propose to use site-directed mutagenesis of a cloned HA gene and cell-free acyltransferase assays using synthetic peptide substrates to identify fundamental structural requirements for protein fatty acid acylation and to characterize the functional role of fatty acid in membrane fusion and budding. These experiments are designed to test the hypothesis that fatty acid on the HA can significantly influence structural or biological properties of the molecule. The results obtained will increase our understanding of this important human pathogen and also improve our view of a widespread post-translational modification beyond the virological context to many cell proteins.