Structural basis of glycan276-dependent recognition by HIV-1 broadly neutralizing antibodies
Summary: Recognition of N-linked glycan at residue N276 (glycan276) at the periphery of the CD4-binding site (CD4bs) on the HIV-envelope trimer is a formidable challenge for many CD4bs-directed antibodies. To understand how this glycan can be recognized, here we isolate two lineages of glycan276-dep...
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| Format: | Article |
| Language: | English |
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Elsevier
2021-11-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124721013954 |
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| author | Christopher A. Cottrell Kartik Manne Rui Kong Shuishu Wang Tongqing Zhou Gwo-Yu Chuang Robert J. Edwards Rory Henderson Katarzyna Janowska Megan Kopp Bob C. Lin Mark K. Louder Adam S. Olia Reda Rawi Chen-Hsiang Shen Justin D. Taft Jonathan L. Torres Nelson R. Wu Baoshan Zhang Nicole A. Doria-Rose Myron S. Cohen Barton F. Haynes Lawrence Shapiro Andrew B. Ward Priyamvada Acharya John R. Mascola Peter D. Kwong |
| author_facet | Christopher A. Cottrell Kartik Manne Rui Kong Shuishu Wang Tongqing Zhou Gwo-Yu Chuang Robert J. Edwards Rory Henderson Katarzyna Janowska Megan Kopp Bob C. Lin Mark K. Louder Adam S. Olia Reda Rawi Chen-Hsiang Shen Justin D. Taft Jonathan L. Torres Nelson R. Wu Baoshan Zhang Nicole A. Doria-Rose Myron S. Cohen Barton F. Haynes Lawrence Shapiro Andrew B. Ward Priyamvada Acharya John R. Mascola Peter D. Kwong |
| author_sort | Christopher A. Cottrell |
| collection | DOAJ |
| description | Summary: Recognition of N-linked glycan at residue N276 (glycan276) at the periphery of the CD4-binding site (CD4bs) on the HIV-envelope trimer is a formidable challenge for many CD4bs-directed antibodies. To understand how this glycan can be recognized, here we isolate two lineages of glycan276-dependent CD4bs antibodies. Antibody CH540-VRC40.01 (named for donor-lineage.clone) neutralizes 81% of a panel of 208 diverse strains, while antibody CH314-VRC33.01 neutralizes 45%. Cryo-electron microscopy (cryo-EM) structures of these two antibodies and 179NC75, a previously identified glycan276-dependent CD4bs antibody, in complex with HIV-envelope trimer reveal substantially different modes of glycan276 recognition. Despite these differences, binding of glycan276-dependent antibodies maintains a glycan276 conformation similar to that observed in the absence of glycan276-binding antibodies. By contrast, glycan276-independent CD4bs antibodies, such as VRC01, displace glycan276 upon binding. These results provide a foundation for understanding antibody recognition of glycan276 and suggest its presence may be crucial for priming immunogens seeking to initiate broad CD4bs recognition. |
| first_indexed | 2024-12-20T17:48:59Z |
| format | Article |
| id | doaj.art-0dffdf01c46c4651a77c53c885d4f689 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-20T17:48:59Z |
| publishDate | 2021-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-0dffdf01c46c4651a77c53c885d4f6892022-12-21T19:30:53ZengElsevierCell Reports2211-12472021-11-01375109922Structural basis of glycan276-dependent recognition by HIV-1 broadly neutralizing antibodiesChristopher A. Cottrell0Kartik Manne1Rui Kong2Shuishu Wang3Tongqing Zhou4Gwo-Yu Chuang5Robert J. Edwards6Rory Henderson7Katarzyna Janowska8Megan Kopp9Bob C. Lin10Mark K. Louder11Adam S. Olia12Reda Rawi13Chen-Hsiang Shen14Justin D. Taft15Jonathan L. Torres16Nelson R. Wu17Baoshan Zhang18Nicole A. Doria-Rose19Myron S. Cohen20Barton F. Haynes21Lawrence Shapiro22Andrew B. Ward23Priyamvada Acharya24John R. Mascola25Peter D. Kwong26IAVI Neutralizing Antibody Center, Consortium for HIV/AIDS Vaccine Development (CHAVD), Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USADuke University Human Vaccine Institute, Departments of Medicine and Surgery, Duke University School of Medicine, Durham, NC 27710, USA; Center for HIV/AIDS Vaccine Immunology-Immunogen Discovery at Duke University, Durham, NC 27710, 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, USADuke University Human Vaccine Institute, Departments of Medicine and Surgery, Duke University School of Medicine, Durham, NC 27710, USA; Center for HIV/AIDS Vaccine Immunology-Immunogen Discovery at Duke University, Durham, NC 27710, USADuke University Human Vaccine Institute, Departments of Medicine and Surgery, Duke University School of Medicine, Durham, NC 27710, USA; Center for HIV/AIDS Vaccine Immunology-Immunogen Discovery at Duke University, Durham, NC 27710, USADuke University Human Vaccine Institute, Departments of Medicine and Surgery, Duke University School of Medicine, Durham, NC 27710, USA; Center for HIV/AIDS Vaccine Immunology-Immunogen Discovery at Duke University, Durham, NC 27710, USADuke University Human Vaccine Institute, Departments of Medicine and Surgery, Duke University School of Medicine, Durham, NC 27710, USA; Center for HIV/AIDS Vaccine Immunology-Immunogen Discovery at Duke University, Durham, NC 27710, 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, USAIAVI Neutralizing Antibody Center, Consortium for HIV/AIDS Vaccine Development (CHAVD), Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USAIAVI Neutralizing Antibody Center, Consortium for HIV/AIDS Vaccine Development (CHAVD), Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, 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, USADepartments of Medicine, Epidemiology, and Microbiology, University of North Carolina-Chapel Hill, Chapel Hill, NC 27599, USADuke University Human Vaccine Institute, Departments of Medicine and Surgery, Duke University School of Medicine, Durham, NC 27710, USA; Center for HIV/AIDS Vaccine Immunology-Immunogen Discovery at Duke University, Durham, NC 27710, 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, USAIAVI Neutralizing Antibody Center, Consortium for HIV/AIDS Vaccine Development (CHAVD), Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USADuke University Human Vaccine Institute, Departments of Medicine and Surgery, Duke University School of Medicine, Durham, NC 27710, USA; Center for HIV/AIDS Vaccine Immunology-Immunogen Discovery at Duke University, Durham, NC 27710, USA; Vaccine 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; Corresponding authorVaccine 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: Recognition of N-linked glycan at residue N276 (glycan276) at the periphery of the CD4-binding site (CD4bs) on the HIV-envelope trimer is a formidable challenge for many CD4bs-directed antibodies. To understand how this glycan can be recognized, here we isolate two lineages of glycan276-dependent CD4bs antibodies. Antibody CH540-VRC40.01 (named for donor-lineage.clone) neutralizes 81% of a panel of 208 diverse strains, while antibody CH314-VRC33.01 neutralizes 45%. Cryo-electron microscopy (cryo-EM) structures of these two antibodies and 179NC75, a previously identified glycan276-dependent CD4bs antibody, in complex with HIV-envelope trimer reveal substantially different modes of glycan276 recognition. Despite these differences, binding of glycan276-dependent antibodies maintains a glycan276 conformation similar to that observed in the absence of glycan276-binding antibodies. By contrast, glycan276-independent CD4bs antibodies, such as VRC01, displace glycan276 upon binding. These results provide a foundation for understanding antibody recognition of glycan276 and suggest its presence may be crucial for priming immunogens seeking to initiate broad CD4bs recognition.http://www.sciencedirect.com/science/article/pii/S2211124721013954antibody-antigen bindingantibody approach angleCD4 binding sitecryo-EMglycan conformationglycan276 |
| spellingShingle | Christopher A. Cottrell Kartik Manne Rui Kong Shuishu Wang Tongqing Zhou Gwo-Yu Chuang Robert J. Edwards Rory Henderson Katarzyna Janowska Megan Kopp Bob C. Lin Mark K. Louder Adam S. Olia Reda Rawi Chen-Hsiang Shen Justin D. Taft Jonathan L. Torres Nelson R. Wu Baoshan Zhang Nicole A. Doria-Rose Myron S. Cohen Barton F. Haynes Lawrence Shapiro Andrew B. Ward Priyamvada Acharya John R. Mascola Peter D. Kwong Structural basis of glycan276-dependent recognition by HIV-1 broadly neutralizing antibodies Cell Reports antibody-antigen binding antibody approach angle CD4 binding site cryo-EM glycan conformation glycan276 |
| title | Structural basis of glycan276-dependent recognition by HIV-1 broadly neutralizing antibodies |
| title_full | Structural basis of glycan276-dependent recognition by HIV-1 broadly neutralizing antibodies |
| title_fullStr | Structural basis of glycan276-dependent recognition by HIV-1 broadly neutralizing antibodies |
| title_full_unstemmed | Structural basis of glycan276-dependent recognition by HIV-1 broadly neutralizing antibodies |
| title_short | Structural basis of glycan276-dependent recognition by HIV-1 broadly neutralizing antibodies |
| title_sort | structural basis of glycan276 dependent recognition by hiv 1 broadly neutralizing antibodies |
| topic | antibody-antigen binding antibody approach angle CD4 binding site cryo-EM glycan conformation glycan276 |
| url | http://www.sciencedirect.com/science/article/pii/S2211124721013954 |
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