8F3A

HIV-1 gp41 coiled-coil pocket IQN17

Summary for 8F3A

• Entry DOI: 10.2210/pdb8f3a/pdb
• Descriptor: IQN17, ACETIC ACID, CHLORIDE ION, ... (4 entities in total)
• Functional Keywords: hiv-1, gp41, coiled-coil, pocket, viral protein
• Biological source: HIV-1 M:B_HXB2R
• Total number of polymer chains: 3
• Total formula weight: 16537.22

Authors

Bruun, T.U.J.,Tang, S.,Fernandez, D.,Kim, P.S. (deposition date: 2022-11-09, release date: 2023-03-08, Last modification date: 2023-10-25)

Primary citation

Bruun, T.U.J.,Tang, S.,Erwin, G.,Deis, L.,Fernandez, D.,Kim, P.S.
Structure-guided stabilization improves the ability of the HIV-1 gp41 hydrophobic pocket to elicit neutralizing antibodies.
J.Biol.Chem., 299:103062-103062, 2023

PubMed Abstract: The hydrophobic pocket found in the N-heptad repeat (NHR) region of HIV-1 gp41 is a highly conserved epitope that is the target of various HIV-1-neutralizing monoclonal antibodies. Although the high conservation of the pocket makes it an attractive vaccine candidate, it has been challenging to elicit potent anti-NHR antibodies via immunization. Here, we solved a high-resolution structure of the NHR mimetic IQN17, and, consistent with previous ligand-bound gp41 pocket structures, we observed remarkable conformational plasticity of the pocket. The high malleability of this pocket led us to test whether we could improve the immunogenicity of the gp41 pocket by stabilizing its conformation. We show that the addition of five amino acids at the C terminus of IQN17, to generate IQN22, introduces a stabilizing salt bridge at the base of the peptide that rigidifies the pocket. Mice immunized with IQN22 elicited higher avidity antibodies against the gp41 pocket and a more potent, albeit still weak, neutralizing response against HIV-1 compared with IQN17. Stabilized epitope-focused immunogens could serve as the basis for future HIV-1 fusion-inhibiting vaccines.

PubMed: 36841484
DOI: 10.1016/j.jbc.2023.103062

Experimental method

X-RAY DIFFRACTION (1.2 Å)