Dynamic allostery governs cyclophilin A–HIV capsid interplay
Lu M., Hou G., Zhang H., Suiter CL., Ahn J., Byeon I-JL., Perilla JR., Langmead CJ., Hung I., Gor'kov PL., Gan Z., Brey W., Aiken C., Zhang P., Schulten K., Gronenborn AM., Polenova T.
Significance The mechanisms of how Cyclophilin A (CypA) regulates HIV-1 infectivity remain poorly understood. We examined the role of dynamics in capsid (CA) protein assemblies by magic-angle-spinning NMR. The assembled CA is highly dynamic. Dipolar tensors calculated from molecular dynamics trajectories are in quantitative agreement with the NMR results. Motions in the CypA loop are sequence-dependent and attenuated in the escape mutants A92E and G94D. Dynamics are similar in escape mutants and CA/CypA complex. These findings suggest that CA escapes from CypA dependence through dynamic allostery. Thus, a host factor's function in HIV infectivity may not be primarily associated with a structural change of the capsid core, but with altering its dynamics, such as the reduction of motions for the CypA loop.