6MNQ

Rhesus macaque anti-HIV V3 antibody DH727.2 with gp120 V3 ZAM18 peptide

Summary for 6MNQ

• Entry DOI: 10.2210/pdb6mnq/pdb
• Descriptor: Envelope glycoprotein, Ab DH727.2 heavy chain Fab fragment, Ab DH727.2 light chain, ... (5 entities in total)
• Functional Keywords: hiv-1 gp120 v3 antibody, immune system
• Biological source: Macaca mulatta; More
• Total number of polymer chains: 3
• Total formula weight: 50000.75

Authors

Nicely, N.I. (deposition date: 2018-10-02, release date: 2019-07-24, Last modification date: 2024-11-13)

Primary citation

Han, Q.,Jones, J.A.,Nicely, N.I.,Reed, R.K.,Shen, X.,Mansouri, K.,Louder, M.,Trama, A.M.,Alam, S.M.,Edwards, R.J.,Bonsignori, M.,Tomaras, G.D.,Korber, B.,Montefiori, D.C.,Mascola, J.R.,Seaman, M.S.,Haynes, B.F.,Saunders, K.O.
Difficult-to-neutralize global HIV-1 isolates are neutralized by antibodies targeting open envelope conformations.
Nat Commun, 10:2898-2898, 2019

PubMed Abstract: The HIV-1 envelope (Env) is the target for neutralizing antibodies and exists on the surface of virions in open or closed conformations. Difficult-to-neutralize viruses (tier 2) express Env in a closed conformation antigenic for broadly neutralizing antibodies (bnAbs) but not for third variable region (V3) antibodies. Here we show that select V3 macaque antibodies elicited by Env vaccination can neutralize 26% of otherwise tier 2 HIV-1 isolates in standardized virus panels. The V3 antibodies only bound to Env in its open conformation. Thus, Envs on tier 2 viruses sample a state where the V3 loop is not in its closed conformation position. Envelope second variable region length, glycosylation sites and V3 amino acids were signatures of neutralization sensitivity. This study determined that open conformations of Env with V3 exposed are present on a subset of otherwise neutralization-resistant virions, therefore neutralization of tier 2 HIV-1 does not always indicate bnAb induction.

PubMed: 31263112
DOI: 10.1038/s41467-019-10899-2

Experimental method

X-RAY DIFFRACTION (1.804 Å)