6CXG

anti-HIV-1 Fab 2G12 in complex with glycopeptide 10V1S

Summary for 6CXG

• Entry DOI: 10.2210/pdb6cxg/pdb
• Descriptor: anti-HIV-1 Fab 2G12 light chain, anti-HIV-1 Fab 2g12 heavy chain, 10V1S glycopeptide, ... (7 entities in total)
• Functional Keywords: antibody, glycopeptide, hiv-1, glycobiology, immune system
• Biological source: Homo sapiens; More
• Total number of polymer chains: 6
• Total formula weight: 107087.30

Authors

Stanfield, R.L.,Wilson, I.A. (deposition date: 2018-04-03, release date: 2019-02-20, Last modification date: 2023-10-04)

Primary citation

Nguyen, D.N.,Xu, B.,Stanfield, R.L.,Bailey, J.K.,Horiya, S.,Temme, J.S.,Leon, D.R.,LaBranche, C.C.,Montefiori, D.C.,Costello, C.E.,Wilson, I.A.,Krauss, I.J.
Oligomannose Glycopeptide Conjugates Elicit Antibodies Targeting the Glycan Core Rather than Its Extremities.
ACS Cent Sci, 5:237-249, 2019

PubMed Abstract: Up to ∼20% of HIV-infected individuals eventually develop broadly neutralizing antibodies (bnAbs), and many of these antibodies (∼40%) target a region of dense high-mannose glycosylation on gp120 of the HIV envelope protein, known as the "high-mannose patch" (HMP). Thus, there have been numerous attempts to develop glycoconjugate vaccine immunogens that structurally mimic the HMP and might elicit bnAbs targeting this conserved neutralization epitope. Herein, we report on the immunogenicity of glycopeptides, designed by selection, that bind tightly to anti-HMP antibody 2G12. By analyzing the fine carbohydrate specificity of rabbit antibodies elicited by these immunogens, we found that they differ from some natural human bnAbs, such as 2G12 and PGT128, in that they bind primarily to the core structures within the glycan, rather than to the Manα1 → 2Man termini (2G12) or to the whole glycan (PGT128). Antibody specificity for the glycan core may result from extensive serum mannosidase trimming of the immunogen in the vaccinated animals. This finding has broad implications for vaccine design aiming to target glycan-dependent HIV neutralizing antibodies.

PubMed: 30834312
DOI: 10.1021/acscentsci.8b00588

Experimental method

X-RAY DIFFRACTION (2.298 Å)