7RDW

Crystal Structure of FH1 Fab bound to HXb2 HIV-1 gp120 core

Summary for 7RDW

• Entry DOI: 10.2210/pdb7rdw/pdb
• Descriptor: Glycoprotein 120, FH1 Fab Heavy Chain, FH1 Fab Light Chain, ... (10 entities in total)
• Functional Keywords: fh1, vh1-2*02, vrc01, antibody, hiv-1, immune system
• Biological source: Human immunodeficiency virus 1; More
• Total number of polymer chains: 12
• Total formula weight: 365285.29

Authors

Weidle, C.,Pancera, M. (deposition date: 2021-07-12, release date: 2022-05-25, Last modification date: 2024-10-23)

Primary citation

Gray, M.D.,Feng, J.,Weidle, C.E.,Cohen, K.W.,Ballweber-Fleming, L.,MacCamy, A.J.,Huynh, C.N.,Trichka, J.J.,Montefiori, D.,Ferrari, G.,Pancera, M.,McElrath, M.J.,Stamatatos, L.
Characterization of a vaccine-elicited human antibody with sequence homology to VRC01-class antibodies that binds the C1C2 gp120 domain.
Sci Adv, 8:eabm3948-eabm3948, 2022

PubMed Abstract: Broadly HIV-1-neutralizing VRC01-class antibodies bind the CD4-binding site of Env and contain V1-2*02-derived heavy chains paired with light chains expressing five-amino acid-long CDRL3s. Their unmutated germline forms do not recognize HIV-1 Env, and their lack of elicitation in human clinical trials could be due to the absence of activation of the corresponding naïve B cells by the vaccine immunogens. To address this point, we examined Env-specific B cell receptor sequences from participants in the HVTN 100 clinical trial. Of all the sequences analyzed, only one displayed homology to VRC01-class antibodies, but the corresponding antibody (FH1) recognized the C1C2 gp120 domain. For FH1 to switch epitope recognition to the CD4-binding site, alterations in the CDRH3 and CDRL3 were necessary. Only germ line-targeting Env immunogens efficiently activated VRC01 B cells, even in the presence of FH1 B cells. Our findings support the use of these immunogens to activate VRC01 B cells in humans.

PubMed: 35507661
DOI: 10.1126/sciadv.abm3948

Experimental method

X-RAY DIFFRACTION (3.55 Å)