National Institutes of Health/National Institute of General Medical Sciences
R01-GM112508
米国
National Institutes of Health/National Institute of General Medical Sciences
P50-GM082545
米国
National Institutes of Health/National Institute Of Allergy and Infectious Diseases
R01-AI150479
米国
National Institutes of Health/National Institute Of Allergy and Infectious Diseases
P50-AI150464
米国
引用
ジャーナル: Sci Adv / 年: 2019 タイトル: Hierarchical assembly governs TRIM5α recognition of HIV-1 and retroviral capsids. 著者: Katarzyna A Skorupka / Marcin D Roganowicz / Devin E Christensen / Yueping Wan / Owen Pornillos / Barbie K Ganser-Pornillos / 要旨: TRIM5α is a restriction factor that senses incoming retrovirus cores through an unprecedented mechanism of nonself recognition. TRIM5α assembles a hexagonal lattice that avidly binds the capsid ...TRIM5α is a restriction factor that senses incoming retrovirus cores through an unprecedented mechanism of nonself recognition. TRIM5α 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 TRIM5α directly contacts the capsid surface have not been established. Here, we apply cryo-electron tomography and subtomogram averaging to determine structures of TRIM5α 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 TRIM5α 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.