期刊
NATURE STRUCTURAL & MOLECULAR BIOLOGY
卷 20, 期 7, 页码 796-+出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/nsmb.2594
关键词
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资金
- Wellcome Trust [WT093378MA, WT099197MA]
- UK Research Councils' Basic Technology Initiative 'Glycoarrays' [GRS/79268]
- UK Engineering and Physical Sciences Research Council Translational grant [EP/G037604/1]
- US National Cancer Institute (NCI) Alliance of Glycobiologists for Detection of Cancer and Cancer Risk [U01 CA128416]
- US National Institutes of Health (NIH) through the National Center for Research Resources' P41 program at the National Center for Research Resources [RR017573]
- NIH [P30 AI036214]
- NIH National Institute of General Medical Sciences (NIGMS)
- Howard Hughes Medical Institute
- Office of Science, Office of Basic Energy Sciences of the US Department of Energy (DOE) [DE-AC02-05CH11231]
- DOE, Basic Energy Sciences, Office of Science [DE-AC02-06CH11357]
- NCI [Y1-CO-1020]
- NIGMS [Y1-GM-1104]
- International AIDS Vaccine Initiative Neutralizing Antibody Center
- Center for HIV/AIDS Vaccine Immunology [CHAVI-ID UM1 AI100663]
- HIV Vaccine Research and Design program [P01 AI82362, R37 AI36082]
- University of California, San Diego, Center for AIDS Research
- NIH, US National Institute of Allergy and Infectious Disease
- NIH, NCI
- NIH, US National Institute of Mental Health
- NIH, US National Institute on Drug Abuse
- NIH, US National Institute of Child Health and Human Development
- NIH, US National Institute of Heart, Lung and Blood
- NIH, US National Institute of Aging
- NIH RO1 grants [AI84817, AI33292]
- Joint Center of Structural Genomics by the NIH NIGMS Protein Structure Initiative [U54 GM094586]
- American Foundation for AIDS Research Mathilde Krim Fellowship in Basic Biomedical Research
- EPSRC [EP/G037604/1] Funding Source: UKRI
- Engineering and Physical Sciences Research Council [GR/S79268/02, EP/G037604/1] Funding Source: researchfish
A substantial proportion of the broadly neutralizing antibodies (bnAbs) identified in certain HIV-infected donors recognize glycan-dependent epitopes on HIV-1 gp120. Here we elucidate how the bnAb PGT 135 binds its Asn332 glycan-dependent epitope from its 3.1-angstrom crystal structure with gp120, CD4 and Fab 17b. PGT 135 interacts with glycans at Asn332, Asn392 and Asn386, using long CDR loops H1 and H3 to penetrate the glycan shield and access the gp120 protein surface. EM reveals that PGT 135 can accommodate the conformational and chemical diversity of gp120 glycans by altering its angle of engagement. Combined structural studies of PGT 135, PGT 128 and 2G12 show that this Asn332-dependent antigenic region is highly accessible and much more extensive than initially appreciated, which allows for multiple binding modes and varied angles of approach; thereby it represents a supersite of vulnerability for antibody neutralization.
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