The HIV capsid undergoes a maturation process where over a thousand of the HIV capsid proteins self assemble into a polymorphic conic shaped shell to enclose the viral genomic materials. Despite of the structural studies, the assembly mechanism is still unclear. We create a coarsed-grain model to capture the overall backbone shape of the capsid protein and apply to simulate the HIV capsid assembly. Our results suggest the interdomain orientation controlled by the subunit dynamics in solution dictates the final assembly morphology and pathway. Specifically, hexameric lattices are formed when the subunits assume a broad range of dimeric conformations observed in solution, with variable minor curvature. Trimers of dimers are observed as the most abundant intermediate oligomers, preceding the hexamer assembly. Sharp curvatured products are formed by coexisting pentamers and hexamers, resembling the ends of authentic conic HIV capsids, only when the subunits assume the conformation identified in pentameric assembly with a specific interdomain orientation. Moreover, the system exhibit entire different profile of assembly intermediates from those of hexameric assembly.

Mechanism of the polymorphism and curvature control of the HIV capsid protein assemblies probed by a novel coarse grain model

2019 Spring National Meeting

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