Studies on Protein Lipidation

项目总结 为了阐明S棕榈酰化IFITM(1，2和3)在宿主抗病毒免疫中的作用机制，我们 建议对这些脂化免疫效应器进行详细的生化、生物物理和细胞研究 这笔拨款续期。对于IFITM的生化和结构研究，我们将进行计算建模 并在体外重组位点特异性脂化的IFITM3(目标1)。此外，我们还发现了直接 IFITMS与特定细胞脂质的相互作用，并将在体外和 在病毒感染期间的哺乳动物细胞(目标2)。最后，我们将研究S与棕榈酰化IFITM的相互作用 关键的细胞因子涉及它们的调节和抗病毒活性(目标3)。这些研究应该会有所帮助 确定IFITM如何阻止病毒入侵，并阐明哪些部位特异的生化机制 在宿主免疫中，脂化作用控制膜蛋白的结构和功能。确定哪些机制 控制S棕榈酰化的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.