Critical mechanistic features of HIV-1 viral capsid assembly.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 36608139.
- Also identified by DOI 10.1126/sciadv.add7434 and PMC identifier 9821859.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
The maturation of HIV-1 capsid protein (CA) into a cone-shaped lattice capsid is critical for viral infectivity. CA can self-assemble into a range of capsid morphologies made of ~175 to 250 hexamers and 12 pentamers. The cellular polyanion inositol hexakisphosphate (IP6) has recently been demonstrated to facilitate conical capsid formation by coordinating a ring of arginine residues within the central cavity of capsid hexamers and pentamers. However, the kinetic interplay of events during IP6 and CA coassembly is unclear. In this work, we use coarse-grained molecular dynamics simulations to elucidate the molecular mechanism of capsid formation, including the role played by IP6. We show that IP6, in small quantities at first, promotes curvature generation by trapping pentameric defects in the growing lattice and shifts assembly behavior toward kinetically favored outcomes. Our analysis also suggests that IP6 can stabilize metastable capsid intermediates and can induce structural pleomorphism in mature capsids.