8TOX

Cryo-EM structure of BG505 Env mutant A517E in complex with antibody ACS202 Fab

This is a non-PDB format compatible entry.

Summary for 8TOX

• Entry DOI: 10.2210/pdb8tox/pdb
• EMDB information: 41461
• Descriptor: Envelope glycoprotein gp41, Envelope glycoprotein gp120, antibody ACS202 Fab heavy chain, ... (10 entities in total)
• Functional Keywords: complex, viral antigen, antibody, viral protein, viral protein-antiviral protein, immune system complex, viral protein/antiviral protein, immune system
• Biological source: Human immunodeficiency virus 1; More
• Total number of polymer chains: 12
• Total formula weight: 389082.90

Authors

Wang, S.,Kwong, P.D. (deposition date: 2023-08-04, release date: 2024-08-14, Last modification date: 2025-02-26)

Primary citation

Reveiz, M.,Xu, K.,Lee, M.,Wang, S.,Olia, A.S.,Harris, D.R.,Liu, K.,Liu, T.,Schaub, A.J.,Stephens, T.,Wang, Y.,Zhang, B.,Huang, R.,Tsybovsky, Y.,Kwong, P.D.,Rawi, R.
Vaccine-elicited and naturally elicited antibodies differ in their recognition of the HIV-1 fusion peptide.
Front Immunol, 15:1484029-1484029, 2024

PubMed Abstract: Broadly neutralizing antibodies have been proposed as templates for HIV-1 vaccine design, but it has been unclear how similar vaccine-elicited antibodies are to their naturally elicited templates. To provide insight, here we compare the recognition of naturally elicited and vaccine-elicited antibodies targeting the HIV-1 fusion peptide, which comprises envelope (Env) residues 512-526, with the most common sequence being AVGIGAVFLGFLGAA. Naturally elicited antibodies bound peptides with substitutions to negatively charged amino acids at residue positions 517-520 substantially better than the most common sequence, despite these substitutions rarely appearing in HIV-1; by contrast, vaccine-elicited antibodies were less tolerant of sequence variation, with no substitution of residues 512-516 showing increased binding. Molecular dynamics analysis and cryo-EM structural analysis of the naturally elicited ACS202 antibody in complex with the HIV-1 Env trimer with an alanine 517 to glutamine substitution suggested enhanced binding to result from electrostatic interactions with positively charged antibody residues. Overall, vaccine-elicited antibodies appeared to be more fully optimized to bind the most common fusion peptide sequence, perhaps reflecting the immunization with fusion peptide of the vaccine-elicited antibodies.

PubMed: 39611147
DOI: 10.3389/fimmu.2024.1484029

Experimental method

ELECTRON MICROSCOPY (2.3 Å)