Structure of Super-Potent Antibody CAP256-VRC26.25 in Complex with HIV-1 Envelope Reveals a Combined Mode of Trimer-Apex Recognition
Summary: Antibodies targeting the V1V2 apex of the HIV-1 envelope (Env) trimer comprise one of the most commonly elicited categories of broadly neutralizing antibodies. Structures of these antibodies indicate diverse modes of Env recognition typified by antibodies of the PG9 class and the PGT145 cla...
| Main Authors: | , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2020-04-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124720303661 |
| _version_ | 1819138731929501696 |
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| author | Jason Gorman Gwo-Yu Chuang Yen-Ting Lai Chen-Hsiang Shen Jeffrey C. Boyington Aliaksandr Druz Hui Geng Mark K. Louder Krisha McKee Reda Rawi Raffaello Verardi Yongping Yang Baoshan Zhang Nicole A. Doria-Rose Bob Lin Penny L. Moore Lynn Morris Lawrence Shapiro John R. Mascola Peter D. Kwong |
| author_facet | Jason Gorman Gwo-Yu Chuang Yen-Ting Lai Chen-Hsiang Shen Jeffrey C. Boyington Aliaksandr Druz Hui Geng Mark K. Louder Krisha McKee Reda Rawi Raffaello Verardi Yongping Yang Baoshan Zhang Nicole A. Doria-Rose Bob Lin Penny L. Moore Lynn Morris Lawrence Shapiro John R. Mascola Peter D. Kwong |
| author_sort | Jason Gorman |
| collection | DOAJ |
| description | Summary: Antibodies targeting the V1V2 apex of the HIV-1 envelope (Env) trimer comprise one of the most commonly elicited categories of broadly neutralizing antibodies. Structures of these antibodies indicate diverse modes of Env recognition typified by antibodies of the PG9 class and the PGT145 class. The mode of recognition, however, has been unclear for the most potent of the V1V2 apex-targeting antibodies, CAP256-VRC26.25 (named for donor-lineage.clone and referred to hereafter as VRC26.25). Here, we determine the cryoelectron microscopy structure at 3.7 Å resolution of the antigen-binding fragment of VRC26.25 in complex with the Env trimer thought to have initiated the lineage. The 36-residue protruding loop of VRC26.25 displays recognition incorporating both strand-C interactions similar to the PG9 class and V1V2 apex insertion similar to the PGT145 class. Structural elements of separate antibody classes can thus intermingle to form a “combined” class, which in this case yields an antibody of extraordinary potency. : Antibody CAP256-VRC26.25 is one of the most potent known HIV-1-neutralizing antibodies. Gorman et al. determine the cryo-EM structure of this antibody in complex with the Env trimer that initiated the antibody lineage. The structure reveals how elements of distinct antibody classes can intermingle to yield an antibody of extraordinary potency. Keywords: broadly neutralizing antibody, HIV-1 envelope trimer, multidonor antibody class, PCT64, PG9, PGDM1400, PGT145, tyrosine sulfation, V1V2 apex recognition |
| first_indexed | 2024-12-22T11:11:26Z |
| format | Article |
| id | doaj.art-f4ce028b484347ca8096f99812e8601a |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-22T11:11:26Z |
| publishDate | 2020-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-f4ce028b484347ca8096f99812e8601a2022-12-21T18:28:09ZengElsevierCell Reports2211-12472020-04-01311Structure of Super-Potent Antibody CAP256-VRC26.25 in Complex with HIV-1 Envelope Reveals a Combined Mode of Trimer-Apex RecognitionJason Gorman0Gwo-Yu Chuang1Yen-Ting Lai2Chen-Hsiang Shen3Jeffrey C. Boyington4Aliaksandr Druz5Hui Geng6Mark K. Louder7Krisha McKee8Reda Rawi9Raffaello Verardi10Yongping Yang11Baoshan Zhang12Nicole A. Doria-Rose13Bob Lin14Penny L. Moore15Lynn Morris16Lawrence Shapiro17John R. Mascola18Peter D. Kwong19Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USAVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USAVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USAVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USAVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USAVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USAVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USAVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USAVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USAVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USAVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USAVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USAVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USAVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USAVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USACenter for HIV and STIs, National Institute for Communicable Diseases of the National Health Laboratory Service (NHLS), Johannesburg 2192, South Africa; Faculty of Health Sciences, University of the Witwatersrand, Johannesburg 2050, South Africa; Centre for the AIDS Programme of Research in South Africa (CAPRISA), University of KwaZulu-Natal, Congella 4013, South AfricaCenter for HIV and STIs, National Institute for Communicable Diseases of the National Health Laboratory Service (NHLS), Johannesburg 2192, South Africa; Faculty of Health Sciences, University of the Witwatersrand, Johannesburg 2050, South Africa; Centre for the AIDS Programme of Research in South Africa (CAPRISA), University of KwaZulu-Natal, Congella 4013, South AfricaVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA; Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USAVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USAVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA; Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA; Corresponding authorSummary: Antibodies targeting the V1V2 apex of the HIV-1 envelope (Env) trimer comprise one of the most commonly elicited categories of broadly neutralizing antibodies. Structures of these antibodies indicate diverse modes of Env recognition typified by antibodies of the PG9 class and the PGT145 class. The mode of recognition, however, has been unclear for the most potent of the V1V2 apex-targeting antibodies, CAP256-VRC26.25 (named for donor-lineage.clone and referred to hereafter as VRC26.25). Here, we determine the cryoelectron microscopy structure at 3.7 Å resolution of the antigen-binding fragment of VRC26.25 in complex with the Env trimer thought to have initiated the lineage. The 36-residue protruding loop of VRC26.25 displays recognition incorporating both strand-C interactions similar to the PG9 class and V1V2 apex insertion similar to the PGT145 class. Structural elements of separate antibody classes can thus intermingle to form a “combined” class, which in this case yields an antibody of extraordinary potency. : Antibody CAP256-VRC26.25 is one of the most potent known HIV-1-neutralizing antibodies. Gorman et al. determine the cryo-EM structure of this antibody in complex with the Env trimer that initiated the antibody lineage. The structure reveals how elements of distinct antibody classes can intermingle to yield an antibody of extraordinary potency. Keywords: broadly neutralizing antibody, HIV-1 envelope trimer, multidonor antibody class, PCT64, PG9, PGDM1400, PGT145, tyrosine sulfation, V1V2 apex recognitionhttp://www.sciencedirect.com/science/article/pii/S2211124720303661 |
| spellingShingle | Jason Gorman Gwo-Yu Chuang Yen-Ting Lai Chen-Hsiang Shen Jeffrey C. Boyington Aliaksandr Druz Hui Geng Mark K. Louder Krisha McKee Reda Rawi Raffaello Verardi Yongping Yang Baoshan Zhang Nicole A. Doria-Rose Bob Lin Penny L. Moore Lynn Morris Lawrence Shapiro John R. Mascola Peter D. Kwong Structure of Super-Potent Antibody CAP256-VRC26.25 in Complex with HIV-1 Envelope Reveals a Combined Mode of Trimer-Apex Recognition Cell Reports |
| title | Structure of Super-Potent Antibody CAP256-VRC26.25 in Complex with HIV-1 Envelope Reveals a Combined Mode of Trimer-Apex Recognition |
| title_full | Structure of Super-Potent Antibody CAP256-VRC26.25 in Complex with HIV-1 Envelope Reveals a Combined Mode of Trimer-Apex Recognition |
| title_fullStr | Structure of Super-Potent Antibody CAP256-VRC26.25 in Complex with HIV-1 Envelope Reveals a Combined Mode of Trimer-Apex Recognition |
| title_full_unstemmed | Structure of Super-Potent Antibody CAP256-VRC26.25 in Complex with HIV-1 Envelope Reveals a Combined Mode of Trimer-Apex Recognition |
| title_short | Structure of Super-Potent Antibody CAP256-VRC26.25 in Complex with HIV-1 Envelope Reveals a Combined Mode of Trimer-Apex Recognition |
| title_sort | structure of super potent antibody cap256 vrc26 25 in complex with hiv 1 envelope reveals a combined mode of trimer apex recognition |
| url | http://www.sciencedirect.com/science/article/pii/S2211124720303661 |
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