TRIM5α self-assembly and compartmentalization of the HIV-1 viral capsid

Abstract

The tripartite-motif protein, TRIM5α, is an innate immune sensor that potently restricts retrovirus infection by binding to human immunodeficiency virus capsids. Higher-ordered oligomerization of this protein forms hexagonally patterned structures that wrap around the viral capsid, despite an anomalously low affinity for the capsid protein (CA). Several studies suggest TRIM5α oligomerizes into a lattice with a symmetry and spacing that matches the underlying capsid, to compensate for the weak affinity, yet little is known about how these lattices form. Using a combination of computational simulations and electron cryotomography imaging, we reveal the dynamical mechanisms by which these lattices selfassemble. Constrained diffusion allows the lattice to reorganize, whereas defects form on highly curved capsid surfaces to alleviate strain and lattice symmetry mismatches. Statistical analysis localizes the TRIM5α binding interface at or near the CypA binding loop of CA. These simulations elucidate the molecular-scale mechanisms of viral capsid cellular compartmentalization by TRIM5α.

Atomic-scale characterization of mature HIV-1 capsid stabilization by inositol hexakisphosphate (IP 6 )

“…It is of note to recognize that the pathways discussed characterize the binding of IP 6 to preformed mature capsid complexes and not the molecular pathways for the co-assembly of CA and IP 6 , which may differ. Further simulations that target the co-assembly of CA and IP 6 will likely require coarse-grained molecular simulation techniques to overcome the long time scale barriers associated with biomolecular assembly phenomena ( 43 , 44 ). The computed thermodynamic quantities, however, are state functions that do not change in response to the particular path taken, so the IP 6 interactions revealed by the ligand density maps are therefore general.…”

Highly Sensitive Polydiacetylene Ensembles for Biosensing and Bioimaging

“…Biomolecule self-assembling is highly implicated in various biologic events through a variety of non-covalent interactions, such as hydrophobic interaction, hydrogen bonds, electrostatic interaction, and metal coordination (Bera et al, 2020;Yu et al, 2020). The self-assembly structures are the basis of forming different complex biological structures (Cao et al, 2020).…”

The RING domain of TRIM69 promotes higher-order assembly

“…For TRIM5, both dimeric Diaz-Griffero et al, 2009) and trimeric Wagner et al, 2016Wagner et al, , 2018 assemblies have been observed via the same interface, suggesting plasticity of the oligomer formed by the Bbox domain. Molecular-dynamics simulations suggest that both oligomers are present during binding to the HIV capsid (Yu et al, 2020).…”