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Asymmetric opening of HIV-1 Env bound to CD4 and a coreceptor-mimicking antibody
The HIV-1 envelope (Env) glycoprotein, a (gp120-gp41)(3) trimer, mediates fusion of viral and host cell membranes after gp120 binding to host receptor CD4. Receptor binding triggers conformational changes allowing coreceptor (CCR5) recognition through CCR5’s tyrosine-sulfated N-terminus, release of...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6899201/ https://www.ncbi.nlm.nih.gov/pubmed/31792452 http://dx.doi.org/10.1038/s41594-019-0344-5 |
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author | Yang, Zhi Wang, Haoqing Liu, Albert Z. Gristick, Harry B. Bjorkman, Pamela J. |
author_facet | Yang, Zhi Wang, Haoqing Liu, Albert Z. Gristick, Harry B. Bjorkman, Pamela J. |
author_sort | Yang, Zhi |
collection | PubMed |
description | The HIV-1 envelope (Env) glycoprotein, a (gp120-gp41)(3) trimer, mediates fusion of viral and host cell membranes after gp120 binding to host receptor CD4. Receptor binding triggers conformational changes allowing coreceptor (CCR5) recognition through CCR5’s tyrosine-sulfated N-terminus, release of the gp41 fusion peptide, and fusion. We present 3.3Å and 3.5Å cryo-EM structures of E51, a tyrosine-sulfated coreceptor-mimicking antibody, complexed with a CD4-bound open HIV-1 native-like Env trimer. Two classes of asymmetric Env interact with E51, revealing tyrosine-sulfated interactions with gp120 mimicking CCR5 interactions, and two conformations of gp120-gp41 protomers (A and B protomers in AAB and ABB trimers) that differ in their degree of CD4-induced trimer opening and induction of changes to the fusion peptide. By integrating the new structural information with previous closed and open envelope trimer structures, we modeled the order of conformational changes on the path to coreceptor binding site exposure and subsequent viral–host cell membrane fusion. |
format | Online Article Text |
id | pubmed-6899201 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
record_format | MEDLINE/PubMed |
spelling | pubmed-68992012020-06-02 Asymmetric opening of HIV-1 Env bound to CD4 and a coreceptor-mimicking antibody Yang, Zhi Wang, Haoqing Liu, Albert Z. Gristick, Harry B. Bjorkman, Pamela J. Nat Struct Mol Biol Article The HIV-1 envelope (Env) glycoprotein, a (gp120-gp41)(3) trimer, mediates fusion of viral and host cell membranes after gp120 binding to host receptor CD4. Receptor binding triggers conformational changes allowing coreceptor (CCR5) recognition through CCR5’s tyrosine-sulfated N-terminus, release of the gp41 fusion peptide, and fusion. We present 3.3Å and 3.5Å cryo-EM structures of E51, a tyrosine-sulfated coreceptor-mimicking antibody, complexed with a CD4-bound open HIV-1 native-like Env trimer. Two classes of asymmetric Env interact with E51, revealing tyrosine-sulfated interactions with gp120 mimicking CCR5 interactions, and two conformations of gp120-gp41 protomers (A and B protomers in AAB and ABB trimers) that differ in their degree of CD4-induced trimer opening and induction of changes to the fusion peptide. By integrating the new structural information with previous closed and open envelope trimer structures, we modeled the order of conformational changes on the path to coreceptor binding site exposure and subsequent viral–host cell membrane fusion. 2019-12-02 2019-12 /pmc/articles/PMC6899201/ /pubmed/31792452 http://dx.doi.org/10.1038/s41594-019-0344-5 Text en Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms |
spellingShingle | Article Yang, Zhi Wang, Haoqing Liu, Albert Z. Gristick, Harry B. Bjorkman, Pamela J. Asymmetric opening of HIV-1 Env bound to CD4 and a coreceptor-mimicking antibody |
title | Asymmetric opening of HIV-1 Env bound to CD4 and a coreceptor-mimicking antibody |
title_full | Asymmetric opening of HIV-1 Env bound to CD4 and a coreceptor-mimicking antibody |
title_fullStr | Asymmetric opening of HIV-1 Env bound to CD4 and a coreceptor-mimicking antibody |
title_full_unstemmed | Asymmetric opening of HIV-1 Env bound to CD4 and a coreceptor-mimicking antibody |
title_short | Asymmetric opening of HIV-1 Env bound to CD4 and a coreceptor-mimicking antibody |
title_sort | asymmetric opening of hiv-1 env bound to cd4 and a coreceptor-mimicking antibody |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6899201/ https://www.ncbi.nlm.nih.gov/pubmed/31792452 http://dx.doi.org/10.1038/s41594-019-0344-5 |
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