title: Sedimentation velocity studies of the high-molecular weight aggregates of the HIV gp41 ectodomain.
abstract: Accumulation of the HIV envelope protein gp41 is observed in the brain tissues of patients suffering from HIV-associated dementia. Previously, we have shown by electron microscopy that the extracellular domain of SIV gp41, which is analogous to that of HIV, forms high-molecular weight aggregates in vitro, and we have postulated that such high-molecular weight aggregates are responsible for neurological damage in a manner similar to protein deposition diseases such as Alzheimer's and the prion diseases. In this manuscript, we have characterized the self-association of the HIV gp41 ectodomain by sedimentation velocity. We show that discreet species of the gp41 high-molecular weight aggregates are present. The maximum population occurs at 20 S, which corresponds to ~5 trimers of gp41, suggesting that five trimers are required for nucleation of the high-molecular weight aggregates. The concentration dependence of the gp41 self-association indicates that it occurs by mass action. The temperature dependence of gp41 self-association suggests that it is driven by entropy, indicating that intermolecular hydrophobic interactions between trimers of gp41 are driving the association.
authors.affiliation: Department of Biochemistry and Molecular Genetics, University of Illinois at Chicago, 900 S. Ashland, Chicago, IL 60607, USA.
authors.forename: Amy
authors.initials: A
authors.lastname: Jacobs
authors.forename: Kari
authors.initials: K
authors.lastname: Hartman
authors.forename: Thomas
authors.initials: T
authors.lastname: Laue
authors.forename: Michael
authors.initials: M
authors.lastname: Caffrey
mesh_terms: D015526:AIDS Dementia Complex / Q000378:metabolism; D015700:HIV Envelope Protein gp41 / Q000737:chemistry* / Q000378:metabolism; D015497:HIV-1 / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D013696:Temperature; D014461:Ultracentrifugation
chemical_list: D015700:HIV Envelope Protein gp41