7N28

Cryo-EM structure of broadly neutralizing V2-apex-targeting antibody J033 in complex with HIV-1 Env

Summary for 7N28

• Entry DOI: 10.2210/pdb7n28/pdb
• EMDB information: 24071 24128
• Descriptor: Envelope glycoprotein gp120, beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, alpha-D-mannopyranose-(1-6)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (17 entities in total)
• Functional Keywords: hiv-1, siv-1, v2-apex, envelope glycoprotein, neutralizing antibody, glycan-dependent, immune system-viral protein complex, immune system/viral protein
• Biological source: Human immunodeficiency virus 1; More
• Total number of polymer chains: 14
• Total formula weight: 439208.36

Authors

Zhou, T.,Gao, F. (deposition date: 2021-05-28, release date: 2022-04-06, Last modification date: 2022-06-22)

Primary citation

Gao, N.,Gai, Y.,Meng, L.,Wang, C.,Wang, W.,Li, X.,Gu, T.,Louder, M.K.,Doria-Rose, N.A.,Wiehe, K.,Nazzari, A.F.,Olia, A.S.,Gorman, J.,Rawi, R.,Wu, W.,Smith, C.,Khant, H.,de Val, N.,Yu, B.,Luo, J.,Niu, H.,Tsybovsky, Y.,Liao, H.,Kepler, T.B.,Kwong, P.D.,Mascola, J.R.,Qin, C.,Zhou, T.,Yu, X.,Gao, F.
Development of Neutralization Breadth against Diverse HIV-1 by Increasing Ab-Ag Interface on V2.
Adv Sci, 9:e2200063-e2200063, 2022

PubMed Abstract: Understanding maturation pathways of broadly neutralizing antibodies (bnAbs) against HIV-1 can be highly informative for HIV-1 vaccine development. A lineage of J038 bnAbs is now obtained from a long-term SHIV-infected macaque. J038 neutralizes 54% of global circulating HIV-1 strains. Its binding induces a unique "up" conformation for one of the V2 loops in the trimeric envelope glycoprotein and is heavily dependent on glycan, which provides nearly half of the binding surface. Their unmutated common ancestor neutralizes the autologous virus. Continuous maturation enhances neutralization potency and breadth of J038 lineage antibodies via expanding antibody-Env contact areas surrounding the core region contacted by germline-encoded residues. Developmental details and recognition features of J038 lineage antibodies revealed here provide a new pathway for elicitation and maturation of V2-targeting bnAbs.

PubMed: 35319830
DOI: 10.1002/advs.202200063

Experimental method

ELECTRON MICROSCOPY (4.2 Å)