Hierarchical assembly governs TRIM5? recognition of HIV-1 and retroviral capsids.

ABSTRACT: TRIM5? is a restriction factor that senses incoming retrovirus cores through an unprecedented mechanism of nonself recognition. TRIM5? assembles a hexagonal lattice that avidly binds the capsid shell, which surrounds and protects the virus core. The extent to which the TRIM lattice can cover the capsid and how TRIM5? directly contacts the capsid surface have not been established. Here, we apply cryo-electron tomography and subtomogram averaging to determine structures of TRIM5? bound to recombinant HIV-1 capsid assemblies. Our data support a mechanism of hierarchical assembly, in which a limited number of basal interaction modes are successively organized in increasingly higher-order structures that culminate in a TRIM5? cage surrounding a retroviral capsid. We further propose that cage formation explains the mechanism of restriction and provides the structural context that links capsid recognition to ubiquitin-dependent processes that disable the retrovirus.

SUBMITTER: Skorupka KA 

PROVIDER: S-EPMC6881174 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature