Studies on Protein Lipidation

项目摘要 为了阐明S-棕榈酰化IFITM（1，2和3）在宿主免疫中抗病毒的机制，我们 建议对这些脂化免疫效应物进行详细的生物化学、生物物理学和细胞研究， 这一轮的续约。对于IFITM的生化和结构研究，我们将进行计算建模 并在体外重建位点特异性脂化的IFITM 3（目的1）。此外，我们还发现， IFITMs与特定细胞脂质的相互作用，并将在体外研究其生物化学意义， 在哺乳动物细胞中的病毒感染（目的2）。最后，我们将研究S-棕榈酰IFITM相互作用 其中关键细胞因子涉及它们的调节和抗病毒活性（Aim 3）。这些研究应该有助于 确定IFITMs如何防止病毒进入，并阐明位点特异性 脂质化控制宿主免疫中的膜蛋白结构和功能。确定 控制S-棕榈酰化IFITMs功能对于理解宿主免疫至关重要，并可能揭示新的策略 用于对抗人类的病毒感染。

PROJECT SUMMARY To elucidate the antiviral mechanism of S-palmitoylated IFITMs (1, 2 and 3) in host immunity against viruses, we propose to perform detailed biochemical, biophysical and cellular studies of these lipidated immune effectors in this grant renewal. For biochemical and structural studies of IFITMs, we will perform computational modeling and reconstitute site-specifically lipidated IFITM3 in vitro (Aim 1). Moreover, we have discovered direct interactions of IFITMs with specific cellular lipids and will investigate their significance biochemically in vitro and in mammalian cells during virus infections (Aim 2). Lastly, we will investigate S-palmitoylated IFITM interactions with key cellular factors involved their regulation and antiviral activity (Aim 3). These studies should help determine how IFITMs prevent virus entry and elucidate biochemical mechanisms by which site-specific lipidation controls membrane protein structure and function in host immunity. Determining the mechanisms that control S-palmitoylated IFITMs function is crucial for understanding host immunity and may reveal new strategies for combatting virus infection in humans.