A dynamic three-step mechanism drives the HIV-1 pre-fusion reaction
Little is known about the intermolecular dynamics and stoichiometry of the interactions of the human immunodeficiency virus type 1 (HIV-1) envelope (Env) protein with its receptors and co-receptors on the host cell surface. Here we analyze timeresolved HIV-1 Env interactions with T-cell surface glyc...
| Main Authors: | , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
Nature Publishing Group
2018
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| _version_ | 1826269282053390336 |
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| author | Iliopoulou, M Nolan, R Alvarez, L Watanabe, Y Coomer, C Jakobsdottir, G Bowden, T Padilla-Parra, S |
| author_facet | Iliopoulou, M Nolan, R Alvarez, L Watanabe, Y Coomer, C Jakobsdottir, G Bowden, T Padilla-Parra, S |
| author_sort | Iliopoulou, M |
| collection | OXFORD |
| description | Little is known about the intermolecular dynamics and stoichiometry of the interactions of the human immunodeficiency virus type 1 (HIV-1) envelope (Env) protein with its receptors and co-receptors on the host cell surface. Here we analyze timeresolved HIV-1 Env interactions with T-cell surface glycoprotein CD4 (CD4) and C-C chemokine receptor type 5 (CCR5) or C-X-C chemokine receptor type 4 (CXCR4) on the surface of cells, by combining multicolor super-resolution localization microscopy (direct stochastic optical reconstruction microscopy) with fluorescence fluctuation spectroscopy imaging. Utilizing the primary isolate JR-FL and laboratory HXB2 strains, we reveal the time-resolved stoichiometry of CD4 and CCR5 or CXCR4 in the prefusion complex with HIV-1 Env. The HIV-1 Env pre-fusion dynamics for both R5- and X4-tropic strains consists of a three-step mechanism, which seems to differ in stoichiometry. Analyses with the monoclonal HIV-1-neutralizing antibody b12 indicate that the mechanism of inhibition differs between JR-FL and HXB2 Env. The molecular insights obtained here identify assemblies of HIV-1 Env with receptors and co-receptors as potential novel targets for inhibitor design. |
| first_indexed | 2024-03-06T21:22:37Z |
| format | Journal article |
| id | oxford-uuid:41fbbc48-a027-4d71-a37d-a47ae3d114ab |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T21:22:37Z |
| publishDate | 2018 |
| publisher | Nature Publishing Group |
| record_format | dspace |
| spelling | oxford-uuid:41fbbc48-a027-4d71-a37d-a47ae3d114ab2022-03-26T14:46:50ZA dynamic three-step mechanism drives the HIV-1 pre-fusion reactionJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:41fbbc48-a027-4d71-a37d-a47ae3d114abEnglishSymplectic Elements at OxfordNature Publishing Group2018Iliopoulou, MNolan, RAlvarez, LWatanabe, YCoomer, CJakobsdottir, GBowden, TPadilla-Parra, SLittle is known about the intermolecular dynamics and stoichiometry of the interactions of the human immunodeficiency virus type 1 (HIV-1) envelope (Env) protein with its receptors and co-receptors on the host cell surface. Here we analyze timeresolved HIV-1 Env interactions with T-cell surface glycoprotein CD4 (CD4) and C-C chemokine receptor type 5 (CCR5) or C-X-C chemokine receptor type 4 (CXCR4) on the surface of cells, by combining multicolor super-resolution localization microscopy (direct stochastic optical reconstruction microscopy) with fluorescence fluctuation spectroscopy imaging. Utilizing the primary isolate JR-FL and laboratory HXB2 strains, we reveal the time-resolved stoichiometry of CD4 and CCR5 or CXCR4 in the prefusion complex with HIV-1 Env. The HIV-1 Env pre-fusion dynamics for both R5- and X4-tropic strains consists of a three-step mechanism, which seems to differ in stoichiometry. Analyses with the monoclonal HIV-1-neutralizing antibody b12 indicate that the mechanism of inhibition differs between JR-FL and HXB2 Env. The molecular insights obtained here identify assemblies of HIV-1 Env with receptors and co-receptors as potential novel targets for inhibitor design. |
| spellingShingle | Iliopoulou, M Nolan, R Alvarez, L Watanabe, Y Coomer, C Jakobsdottir, G Bowden, T Padilla-Parra, S A dynamic three-step mechanism drives the HIV-1 pre-fusion reaction |
| title | A dynamic three-step mechanism drives the HIV-1 pre-fusion reaction |
| title_full | A dynamic three-step mechanism drives the HIV-1 pre-fusion reaction |
| title_fullStr | A dynamic three-step mechanism drives the HIV-1 pre-fusion reaction |
| title_full_unstemmed | A dynamic three-step mechanism drives the HIV-1 pre-fusion reaction |
| title_short | A dynamic three-step mechanism drives the HIV-1 pre-fusion reaction |
| title_sort | dynamic three step mechanism drives the hiv 1 pre fusion reaction |
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