7KDE

BG505 SOSIP.664 in complex with the V3-targeting rhesus macaque antibody 1485 and human gp120-gp41 interface antibody 8ANC195

Summary for 7KDE

• Entry DOI: 10.2210/pdb7kde/pdb
• EMDB information: 22820
• Descriptor: HIV-1 Envelope Glycoprotein BG505 SOSIP.664 gp41, alpha-D-mannopyranose-(1-3)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]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, broadly neutralizing antibody, env, envelope, bg505, bnab, viral protein, viral protein-immune system complex, viral protein/immune system
• Biological source: Human immunodeficiency virus 1 (HIV-1); More
• Total number of polymer chains: 18
• Total formula weight: 533188.53

Authors

Barnes, C.O.,Bjorkman, P.J. (deposition date: 2020-10-08, release date: 2020-10-28, Last modification date: 2024-10-30)

Primary citation

Wang, Z.,Barnes, C.O.,Gautam, R.,Cetrulo Lorenzi, J.C.,Mayer, C.T.,Oliveira, T.Y.,Ramos, V.,Cipolla, M.,Gordon, K.M.,Gristick, H.B.,West, A.P.,Nishimura, Y.,Raina, H.,Seaman, M.S.,Gazumyan, A.,Martin, M.,Bjorkman, P.J.,Nussenzweig, M.C.,Escolano, A.
A broadly neutralizing macaque monoclonal antibody against the HIV-1 V3-Glycan patch.
Elife, 9:-, 2020

PubMed Abstract: A small fraction of HIV-1- infected humans develop broadly neutralizing antibodies (bNAbs) against HIV-1 that protect macaques from simian immunodeficiency HIV chimeric virus (SHIV). Similarly, a small number of macaques infected with SHIVs develop broadly neutralizing serologic activity, but less is known about the nature of simian antibodies. Here, we report on a monoclonal antibody, Ab1485, isolated from a macaque infected with SHIVAD8 that developed broadly neutralizing serologic activity targeting the V3-glycan region of HIV-1 Env. Ab1485 neutralizes 38.1% of HIV-1 isolates in a 42-pseudovirus panel with a geometric mean IC50 of 0.055 µg/mLl and SHIVAD8 with an IC50 of 0.028 µg/mLl. Ab1485 binds the V3-glycan epitope in a glycan-dependent manner. A 3.5 Å cryo-electron microscopy structure of Ab1485 in complex with a native-like SOSIP Env trimer showed conserved contacts with the N332gp120 glycan and gp120 GDIR peptide motif, but in a distinct Env-binding orientation relative to human V3/N332gp120 glycan-targeting bNAbs. Intravenous infusion of Ab1485 protected macaques from a high dose challenge with SHIVAD8. We conclude that macaques can develop bNAbs against the V3-glycan patch that resemble human V3-glycan bNAbs.

PubMed: 33084569
DOI: 10.7554/eLife.61991

Experimental method

ELECTRON MICROSCOPY (3.55 Å)