Conformational changes in cell surface HIV-1 envelope glycoproteins are triggered by cooperation between cell surface CD4 and co-receptors.
We have continuously measured CD4-induced conformational changes of cell surface-expressed human immunodeficiency virus type-1 envelope glycoprotein gp120-gp41 in situ using 4,4'-dianilino-1, 1'-binaphthyl-5,5'-disulfonic acid, a fluorescent probe that binds to hydrophobic groups. CD4-expressing human T cell lines induced significant and rapid conformational changes (<1 min delay) in gp120-gp41 from T cell-tropic strains, and little conformational changes in gp120-gp41 from macrophage-tropic strains, with equivalent levels of envelope expression. Conversely, CD4-expressing human macrophages induced significant and rapid conformational changes in gp120-gp41 from macrophage-tropic strains, and little conformational changes in gp120-gp41 from T cell-tropic strains. Thus, the conformational changes undergone by gp120-gp41, which lead to membrane fusion, are highly cooperative and require both receptor and co-receptor. We used a dye transfer assay to show that neither membrane lipid fusion or fusion pore formation can occur with host cells having different tropism from the envelope.
Jones
P L
PL
Section of Membrane Structure and Function, Laboratory of Experimental and Computational Biology, Division of Basic Sciences, National Cancer Institute, National Institutes of Health, Frederick, Maryland 21702, USA.
Korte
T
T
Blumenthal
R
R
D000817:Anilino Naphthalenesulfonates; D015704:CD4 Antigens / Q000378:metabolism*; D002460:Cell Line; D005456:Fluorescent Dyes; D015699:HIV Envelope Protein gp120 / Q000737:chemistry* / Q000378:metabolism; D015700:HIV Envelope Protein gp41 / Q000737:chemistry* / Q000378:metabolism; D015497:HIV-1 / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D007700:Kinetics; D008561:Membrane Fusion; D011487:Protein Conformation; D015728:Receptors, HIV / Q000378:metabolism*
D000817:Anilino Naphthalenesulfonates; D015704:CD4 Antigens; D005456:Fluorescent Dyes; D015699:HIV Envelope Protein gp120; D015700:HIV Envelope Protein gp41; D015728:Receptors, HIV; C027132:1-anilino-8-naphthalenesulfonate