Project 2: Capsid dynamics and interactions with host factors

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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.