Project 2: Capsid dynamics and interactions with host factors

P2.摘要 在这个项目中，我们将检验我们的假设，该假设是通过在PCHPI进行广泛的研究而建立的，使用了多个 技术，动力学是决定衣壳组装、成熟和相互作用的重要因素 与宿主蛋白结合，如TRIM5α。具体来说，我们将：1)确定构象动力学在CA中的作用 组装体；ii)确定衣壳/TRIM5α动力学并在原子上描绘分子间界面 分辨率；以及iii)确定衣壳/CypA的动力学和CypA诱导的结构扰动 与不同菌株的CA组件结合，显示衣壳稳定性的差异。要完成以下任务 这个项目的具体目标，我们将采用多管齐下的方法，包括MAS核磁共振，冷冻-EM，MD 模拟，以及病毒学和分子生物学方法。我们将结合互补的专业知识 PCHPI调查人员和合作者之间的密切合作，以解决跨学科的问题 关于动态在艾滋病毒-1感染周期中的作用。

P2. Abstract In this project, we will test our hypothesis, established through extensive studies at the PCHPI using multiple techniques, that dynamics are an important factor determining capsid assembly, maturation, and interactions with host proteins, such as TRIM5α. Specifically, we will i) determine the role of conformational dynamics in CA assemblies; ii) determine the capsid/TRIM5α dynamics and delineate the intermolecular interfaces at atomic resolution; and iii) determine the dynamics of capsid/CypA and structural perturbations induced by CypA binding to CA assemblies from different strains exhibiting differences in capsid stability. To accomplish the specific aims of this project, we will employ a multi-pronged approach including MAS NMR, cryo-EM, MD simulations, as well as virology and molecular biology approaches. We will combine the complementary expertise of the PCHPI investigators and collaborators and work in close synergy to tackle the multi-disciplinary questions concerning the role of dynamics in the HIV-1 infection cycle.