Structure of HIV-1 gp41 with its membrane anchors targeted by neutralizing antibodies - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue eLife Année : 2021

Structure of HIV-1 gp41 with its membrane anchors targeted by neutralizing antibodies

Résumé

The HIV-1 gp120/gp41 trimer undergoes a series of conformational changes in order to catalyze gp41-induced fusion of viral and cellular membranes. Here, we present the crystal structure of gp41 locked in a fusion intermediate state by an MPER-specific neutralizing antibody. The structure illustrates the conformational plasticity of the six membrane anchors arranged asymmetrically with the fusion peptides and the transmembrane regions pointing into different directions. Hinge regions located adjacent to the fusion peptide and the transmembrane region facilitate the conformational flexibility that allows high affinity binding of broadly neutralizing anti-MPER antibodies. Molecular dynamics simulation of the MPER Ab-induced gp41 conformation reveals the transition into the final post-fusion conformation with the central fusion peptides forming a hydrophobic core with flanking transmembrane regions. This, thus, suggests that MPER-specific broadly neutralizing antibodies can block final steps of refolding of the fusion peptide and the transmembrane region, which is required for completing membrane fusion.
Fichier principal
Vignette du fichier
2020.11.12.379396.full.pdf (2.04 Mo) Télécharger le fichier
Origine : Fichiers produits par l'(les) auteur(s)

Dates et versions

hal-03102179 , version 1 (07-01-2021)
hal-03102179 , version 2 (11-05-2021)

Identifiants

Citer

Christophe Caillat, Delphine Guilligay, Johana Torralba, Nikolas Friedrich, Jose Nieva, et al.. Structure of HIV-1 gp41 with its membrane anchors targeted by neutralizing antibodies. eLife, 2021, 10 (e65005), ⟨10.1101/2020.11.12.379396⟩. ⟨hal-03102179v1⟩
150 Consultations
56 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More