Design of in vitro symmetric complexes and analysis by hybrid methods reveal mechanisms of HIV capsid assembly.

ABSTRACT: Unlike the capsids of icosahedral viruses, retroviral capsids are pleomorphic, with variably curved, closed fullerene shells composed of ∼250 hexamers and exactly 12 pentamers of the viral CA protein. Structures of CA oligomers have been difficult to obtain because the subunit-subunit interactions are inherently weak, and CA tends to spontaneously assemble into capsid-like particles. Guided by a cryoEM-based model of the hexagonal lattice of HIV-1 CA, we used a two-step biochemical strategy to obtain soluble CA hexamers and pentamers for crystallization. First, each oligomer was stabilized by engineering disulfide cross-links between the N-terminal domains of adjacent subunits. Second, the cross-linked oligomers were prevented from polymerizing into hyperstable, capsid-like structures by m

SUBMITTER: Yeager M 

PROVIDER: S-EPMC3166646 | biostudies-literature | 2011 Jul

REPOSITORIES: biostudies-literature