Structural basis of glycan276-dependent recognition by HIV-1 broadly neutralizing antibodies.

Autor:	Cottrell CA; IAVI 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, USA., Manne K; Duke 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., Kong R; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA., Wang S; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA., Zhou T; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA., Chuang GY; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA., Edwards RJ; Duke 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., Henderson R; Duke 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., Janowska K; Duke 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., Kopp M; Duke 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., Lin BC; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA., Louder MK; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA., Olia AS; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA., Rawi R; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA., Shen CH; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA., Taft JD; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA., Torres JL; IAVI 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, USA., Wu NR; IAVI 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, USA., Zhang B; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA., Doria-Rose NA; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA., Cohen MS; Departments of Medicine, Epidemiology, and Microbiology, University of North Carolina-Chapel Hill, Chapel Hill, NC 27599, USA., Haynes BF; Duke 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., Shapiro L; Vaccine 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., Ward AB; IAVI 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, USA., Acharya P; Duke 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, USA., Mascola JR; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: jmascola@nih.gov., Kwong PD; Vaccine 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. Electronic address: pdkwong@nih.gov.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2021 Nov 02; Vol. 37 (5), pp. 109922.
DOI:	10.1016/j.celrep.2021.109922
Abstrakt:	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. Competing Interests: Declaration of interests The authors declare no competing interests. (Published by Elsevier Inc.)
Databáze:	MEDLINE
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