8F3A

HIV-1 gp41 coiled-coil pocket IQN17

8F3A の概要

• エントリーDOI: 10.2210/pdb8f3a/pdb
• 分子名称: IQN17, ACETIC ACID, CHLORIDE ION, ... (4 entities in total)
• 機能のキーワード: hiv-1, gp41, coiled-coil, pocket, viral protein
• 由来する生物種: HIV-1 M:B_HXB2R
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 16537.22

構造登録者

Bruun, T.U.J.,Tang, S.,Fernandez, D.,Kim, P.S. (登録日: 2022-11-09, 公開日: 2023-03-08, 最終更新日: 2023-10-25)

主引用文献

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

実験手法

X-RAY DIFFRACTION (1.2 Å)