期刊
NATURE STRUCTURAL & MOLECULAR BIOLOGY
卷 23, 期 10, 页码 906-915出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/nsmb.3291
关键词
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资金
- National Institute Of Allergy And Infectious Diseases of the National Institutes of Health [HIVRAD P01 AI100148]
- Bill and Melinda Gates Foundation (Collaboration for AIDS Vaccine Discovery Grant) [OPP1124068]
- Comprehensive Antibody-Vaccine Immune Monitoring Consortium grant [1032144]
- Rockefeller University Center for Clinical and Translational Science grant from the National Center for Advancing Translational Sciences [UL1 TR000043/KL2TR000151]
- Molecular Observatory at Caltech, the Gordon and Betty Moore Foundation
- Heisenberg-Program of the DFG [KL 2389/2-1]
- European Research Council [ERC-StG639961]
- German Center for Infection Research (DZIF), partner site Bonn-Cologne, Cologne, Germany
- US Department of Energy
- National Institutes of Health
HIV-1 vaccine design is informed by structural studies elucidating mechanisms by which broadly neutralizing antibodies (bNAbs) recognize and/or accommodate N-glycans on the trimeric envelope glycoprotein (Env). Variability in high-mannose and complex-type Env glycoforms leads to heterogeneity that usually precludes visualization of the native glycan shield. We present 3.5-angstrom- and 3.9-angstrom-resolution crystal structures of the HIV-1 Env trimer with fully processed and native glycosylation, revealing a glycan shield of high-mannose and complex-type N-glycans, which we used to define complete epitopes of two bNAbs. Env trimer was complexed with 10-1074 (against the V3-loop) and IOMA, a new CD4-binding site (CD4bs) antibody. Although IOMA derives from VH1-2*02, the germline gene of CD4bs-targeting VRC01-class bNAbs, its light chain lacks the short CDRL3 that defines VRC01-class bNAbs. Thus IOMA resembles 8ANC131-class/VH1-46 derived CD4bs bNAbs, which have normal-length CDRL3s. The existence of bNAbs that combine features of VRC01-class and 8ANC131-class antibodies has implications for immunization strategies targeting VRC01-like bNAbs.
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