7UCE

Structure of the anti-HIV-1 neutralizing antibody BG24 Fab fragment

Summary for 7UCE

• Entry DOI: 10.2210/pdb7uce/pdb
• Descriptor: BG24 Fab light chain, BG24 Fab heavy chain, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (4 entities in total)
• Functional Keywords: broadly neutralizing antibody, bnab, hiv-1, cd4 binding site, vh1-2, vrc01-class, antiviral protein, viral protein-immune system complex, viral protein/immune system
• Biological source: Homo sapiens; More
• Total number of polymer chains: 2
• Total formula weight: 47676.04

Authors

Barnes, C.O.,Bjorkman, P.J. (deposition date: 2022-03-16, release date: 2022-08-17, Last modification date: 2024-11-13)

Primary citation

Barnes, C.O.,Schoofs, T.,Gnanapragasam, P.N.P.,Golijanin, J.,Huey-Tubman, K.E.,Gruell, H.,Schommers, P.,Suh-Toma, N.,Lee, Y.E.,Cetrulo Lorenzi, J.C.,Piechocka-Trocha, A.,Scheid, J.F.,West Jr., A.P.,Walker, B.D.,Seaman, M.S.,Klein, F.,Nussenzweig, M.C.,Bjorkman, P.J.
A naturally arising broad and potent CD4-binding site antibody with low somatic mutation.
Sci Adv, 8:eabp8155-eabp8155, 2022

PubMed Abstract: The induction of broadly neutralizing antibodies (bNAbs) is a potential strategy for a vaccine against HIV-1. However, most bNAbs exhibit features such as unusually high somatic hypermutation, including insertions and deletions, which make their induction challenging. VRC01-class bNAbs not only exhibit extraordinary breadth and potency but also rank among the most highly somatically mutated bNAbs. Here, we describe a VRC01-class antibody isolated from a viremic controller, BG24, that is much less mutated than most relatives of its class while achieving comparable breadth and potency. A 3.8-Å x-ray crystal structure of a BG24-BG505 Env trimer complex revealed conserved contacts at the gp120 interface characteristic of the VRC01-class Abs, despite lacking common CDR3 sequence motifs. The existence of moderately mutated CD4-binding site (CD4bs) bNAbs such as BG24 provides a simpler blueprint for CD4bs antibody induction by a vaccine, raising the prospect that such an induction might be feasible with a germline-targeting approach.

PubMed: 35960796
DOI: 10.1126/sciadv.abp8155

Experimental method

X-RAY DIFFRACTION (2.25 Å)