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TitleHierarchical assembly governs TRIM5α recognition of HIV-1 and retroviral capsids.
Journal, issue, pagesSci Adv, Vol. 5, Issue 11, Page eaaw3631, Year 2019
Publish dateNov 27, 2019
AuthorsKatarzyna A Skorupka / Marcin D Roganowicz / Devin E Christensen / Yueping Wan / Owen Pornillos / Barbie K Ganser-Pornillos /
PubMed AbstractTRIM5α 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.
External linksSci Adv / PubMed:31807695 / PubMed Central
MethodsEM (subtomogram averaging) / EM (tomography)
Resolution17.5 - 32.0 Å
Structure data

EMDB-20562:
HIV-1 CA hexamer from TRIM5alpha-coated tubes
Method: EM (subtomogram averaging) / Resolution: 17.5 Å

EMDB-20563:
TRIM5alpha dimer in complex with HIV-1 capsid tubes
Method: EM (tomography)

EMDB-20564:
TRIM5alpha trimer bound to HIV-1 capsid tubes
Method: EM (subtomogram averaging) / Resolution: 24.9 Å

EMDB-20565:
TRIM5alpha lattice bound to HIV-1 capsid lattice
Method: EM (subtomogram averaging) / Resolution: 32.0 Å

EMDB-20574:
TRIM5alpha-coated HIV-1 capsid tube
Method: EM (tomography)

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