title: HIV-1 capsid protein forms spherical (immature-like) and tubular (mature-like) particles in vitro: structure switching by pH-induced conformational changes.
abstract: The viral genome and replicative enzymes of the human immunodeficiency virus are encased in a shell consisting of assembled mature capsid protein (CA). The core shell is a stable, effective protective barrier, but is also poised for dissolution on cue to allow transmission of the viral genome into its new host. In this study, static light scattering (SLS) and dynamic light scattering (DLS) were used to examine the entire range of the CA protein response to an environmental cue (pH). The CA protein assembled tubular structures as previously reported but also was capable of assembling spheres, depending on the pH of the protein solution. The switch from formation of one to the other occurred within a very narrow physiological pH range (i.e., pH 7.0 to pH 6.8). Below this range, only dimers were detected. Above this range, the previously described tubular structures were detected. The ability of the CA protein to form a spherical structure that is detectable by DLS but not by electron microscopy indicates that some assemblages are inherently sensitive to perturbation. The dimers in equilibrium with these assemblages exhibited distinct conformations: Dimers in equilibrium with the spherical form exhibited a compact conformation. Dimers in equilibrium with the rod-like form had an extended conformation. Thus, the CA protein possesses the inherent ability to form metastable structures, the morphology of which is regulated by an environmentally-sensitive molecular switch. Such metastable structures may exist as transient intermediates during the assembly and/or disassembly of the virus core.
authors: Department of Molecular Genetics & Microbiology, State University of New York at Stony Brook, New York 11794, USA.
authors: L S
authors: LS
authors: Ehrlich
authors: T
authors: T
authors: Liu
authors: S
authors: S
authors: Scarlata
authors: B
authors: B
authors: Chu
authors: C A
authors: CA
authors: Carter
mesh_terms: D002213:Capsid / Q000737:chemistry* / Q000378:metabolism* / Q000648:ultrastructure; D019281:Dimerization; D015497:HIV-1 / Q000737:chemistry*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008027:Light; D008854:Microscopy, Electron; D008970:Molecular Weight; D018583:Pliability; D011485:Protein Binding; D020836:Protein Structure, Quaternary; D012542:Scattering, Radiation; D012996:Solutions
chemical_list: D012996:Solutions