9AUI

Cryo-EM structure of CH848.d949.10.17.GS-DH270.UCA4

Summary for 9AUI

• Entry DOI: 10.2210/pdb9aui/pdb
• EMDB information: 43881
• Descriptor: HIV-1 BG505 DS-SOSIP glycoprotein gp120, HIV-1 BG505 DS-SOSIP glycoprotein gp41, UCA4 heavy chain, ... (9 entities in total)
• Functional Keywords: envelope, glycoprotein, trimer, antibody, viral protein, viral protein-immune system complex, viral protein/immune system
• Biological source: Human immunodeficiency virus 1; More
• Total number of polymer chains: 12
• Total formula weight: 369168.74

Authors

Zhang, Q.E.,Acharya, P. (deposition date: 2024-02-29, release date: 2025-02-05)

Primary citation

Swanson, O.M.,Zhang, Q.E.,Van Itallie, E.,Tian, M.,Brown, A.R.,Harris, C.,Kapingidza, A.B.,Rhodes, B.,Smith, L.M.,Venkatayogi, S.,Cronin, K.,Frazier, M.,Parks, R.,Bar, M.,Jiang, C.,Martin Beem, J.S.,Cheng, H.L.,Davis, J.,McGovern, K.,Newman, A.,Edwards, R.J.,Cain, D.,Alam, S.M.,Wiehe, K.,Saunders, K.O.,Acharya, P.,Alt, F.,Haynes, B.F.,Azoitei, M.L.
An engineered immunogen activates diverse HIV broadly neutralizing antibody precursors and promotes acquisition of improbable mutations.
Sci Transl Med, 17:eadr2218-eadr2218, 2025

PubMed Abstract: Elicitation of HIV broadly neutralizing antibodies (bnAbs) by vaccination first requires the activation of diverse precursors, followed by successive boosts that guide these responses to enhanced breadth through the acquisition of somatic mutations. Because HIV bnAbs contain mutations in their B cell receptors (BCRs) that are rarely generated during conventional B cell maturation, HIV vaccine immunogens must robustly engage and expand B cells with BCRs that contain these improbable mutations. Here, we engineered an immunogen that activates diverse precursors of an HIV V3-glycan bnAb and promotes their acquisition of a functionally critical improbable mutation. This immunogen was validated biochemically, structurally, and in three different humanized immunoglobulin mouse models that were designed to test HIV immunogens. These results provide a blueprint for rationally designing priming immunogens that explicitly target the elicitation of antibodies with functional yet improbable mutations.

PubMed: 39772772
DOI: 10.1126/scitranslmed.adr2218

Experimental method

ELECTRON MICROSCOPY (3.8 Å)