Author Description

Another main focus of this dissertation is to understand the interaction of HIV-1 capsid and a host cell factor cyclophilin A (CypA) better. CypA is packaged in the HIV-1 virions, and it directly binds with the HIV-1 capsid and modulates viral infectivity through an unknown mechanism. We have addressed the role of conformational dynamics on the nanosecond to millisecond timescales in the escape from CypA dependence, by MAS NMR and molecular dynamics. 1H-15N and 1H-13C dipolar order parameters (S) obtained from MAS NMR experiments on CA assemblies, CypA escape mutants A92E and G94D, and CA/CypA assemblies are in quantitative agreement with those calculated from MD trajectories. Our data demonstrated that CA assemblies are dynamic on multiple timescales, especially in the CypA binding loop. These motions are significantly reduced in CA/CypA assemblies. Remarkably, the CypA escape mutant assemblies exhibit dynamic behavior similar to that of the CA/CypA assemblies. Together, these findings suggest that a dynamic allostery mechanism governs the CA escape from CypA dependence.