دورية أكاديمية
Glycan clustering stabilizes the mannose patch of HIV-1 and preserves vulnerability to broadly neutralizing antibodies.
العنوان: | Glycan clustering stabilizes the mannose patch of HIV-1 and preserves vulnerability to broadly neutralizing antibodies. |
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المؤلفون: | Pritchard LK; Oxford Glycobiology Institute, Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK., Spencer DI; Ludger Ltd., Culham Science Centre, Abingdon, Oxfordshire OX14 3EB, UK., Royle L; Ludger Ltd., Culham Science Centre, Abingdon, Oxfordshire OX14 3EB, UK., Bonomelli C; Oxford Glycobiology Institute, Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK., Seabright GE; Oxford Glycobiology Institute, Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK., Behrens AJ; Oxford Glycobiology Institute, Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK., Kulp DW; 1] Department of Immunology and Microbial Science and IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, California 92037, USA [2] Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, California 92037, USA., Menis S; 1] Department of Immunology and Microbial Science and IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, California 92037, USA [2] Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, California 92037, USA., Krumm SA; King's College London School of Medicine at Guy's, King's and St Thomas' Hospitals, Guy's Hospital, Great Maze Pond, London SE1 9RT, UK., Dunlop DC; Oxford Glycobiology Institute, Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK., Crispin DJ; Oxford Glycobiology Institute, Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK., Bowden TA; Division of Structural Biology, Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK., Scanlan CN; Oxford Glycobiology Institute, Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK., Ward AB; Department of Integrative Structural and Computational Biology, IAVI Neutralizing Antibody Center, Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA., Schief WR; 1] Department of Immunology and Microbial Science and IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, California 92037, USA [2] Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, California 92037, USA [3] Ragon Institute of MGH, MIT and Harvard, Cambridge, Massachusetts 02139, USA., Doores KJ; King's College London School of Medicine at Guy's, King's and St Thomas' Hospitals, Guy's Hospital, Great Maze Pond, London SE1 9RT, UK., Crispin M; Oxford Glycobiology Institute, Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK. |
المصدر: | Nature communications [Nat Commun] 2015 Jun 24; Vol. 6, pp. 7479. Date of Electronic Publication: 2015 Jun 24. |
نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
اللغة: | English |
بيانات الدورية: | Publisher: Nature Pub. Group Country of Publication: England NLM ID: 101528555 Publication Model: Electronic Cited Medium: Internet ISSN: 2041-1723 (Electronic) Linking ISSN: 20411723 NLM ISO Abbreviation: Nat Commun Subsets: MEDLINE |
أسماء مطبوعة: | Original Publication: [London] : Nature Pub. Group |
مواضيع طبية MeSH: | Antibodies, Neutralizing/*immunology , HIV Envelope Protein gp120/*immunology , HIV-1/*immunology , Mannose/*immunology , Polysaccharides/*immunology, Enzyme-Linked Immunosorbent Assay ; Glycosylation ; HEK293 Cells ; HIV Envelope Protein gp120/genetics ; HIV Envelope Protein gp120/metabolism ; HIV-1/genetics ; HIV-1/metabolism ; Humans ; Mannose/metabolism ; Mass Spectrometry ; Mutagenesis, Site-Directed |
مستخلص: | The envelope spike of HIV-1 employs a 'glycan shield' to protect itself from antibody-mediated neutralization. Paradoxically, however, potent broadly neutralizing antibodies (bnAbs) that target this shield have been isolated. The unusually high glycan density on the gp120 subunit limits processing during biosynthesis, leaving a region of under-processed oligomannose-type structures, which is a primary target of these bnAbs. Here we investigate the contribution of individual glycosylation sites in the formation of this so-called intrinsic mannose patch. Deletion of individual sites has a limited effect on the overall size of the intrinsic mannose patch but leads to changes in the processing of neighbouring glycans. These structural changes are largely tolerated by a panel of glycan-dependent bnAbs targeting these regions, indicating a degree of plasticity in their recognition. These results support the intrinsic mannose patch as a stable target for vaccine design. |
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معلومات مُعتمدة: | UM1 AI100663 United States AI NIAID NIH HHS; R01 AI081625 United States AI NIAID NIH HHS; 1UM1AI100663 United States AI NIAID NIH HHS; 090532 United Kingdom WT_ Wellcome Trust; P01AI081625 United States AI NIAID NIH HHS; MR/K024426/1 United Kingdom MRC_ Medical Research Council; MR/L009528/1 United Kingdom WT_ Wellcome Trust; MR/L009528/1 United Kingdom MRC_ Medical Research Council; United Kingdom WT_ Wellcome Trust |
فهرسة مساهمة: | Indexing Agency: NLM Local ID #: EMS63449. |
المشرفين على المادة: | 0 (Antibodies, Neutralizing) 0 (HIV Envelope Protein gp120) 0 (Polysaccharides) PHA4727WTP (Mannose) |
تواريخ الأحداث: | Date Created: 20150625 Date Completed: 20160405 Latest Revision: 20220129 |
رمز التحديث: | 20221213 |
مُعرف محوري في PubMed: | PMC4500839 |
DOI: | 10.1038/ncomms8479 |
PMID: | 26105115 |
قاعدة البيانات: | MEDLINE |
تدمد: | 2041-1723 |
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DOI: | 10.1038/ncomms8479 |