Structural Basis for Broad HIV-1 Neutralization by a Novel MPER-Specific Human Broadly Neutralizing Antibody - Groupe Entrée et bourgeonnement des virus à enveloppe / Entry and Budding of Enveloped Viruses Group (EBEV) Access content directly
Journal Articles Cell Host and Microbe Year : 2019

Structural Basis for Broad HIV-1 Neutralization by a Novel MPER-Specific Human Broadly Neutralizing Antibody

Andrea Minola
  • Function : Author
Antonio Lanzavecchia
  • Function : Author
  • PersonId : 881203
Davide Corti
  • Function : Author
Giuseppe Pantaleo
Winfried Weissenhorn

Abstract

Potent and broadly neutralizing antibodies (bnAbs) are the hallmark of HIV-1 protection by vaccination. The membrane-proximal external region (MPER) of the HIV-1 gp41 fusion protein is targeted by the most broadly reactive HIV-1 neutralizing antibodies. Here, we examine the structural and molecular mechansims of neutralization by anti-MPER bnAb, LN01, which was isolated from lymph-node-derived germinal center B cells of an elite controller and exhibits broad neutralization breadth. LN01 engages both MPER and the transmembrane (TM) region, which together form a continuous helix in complex with LN01. The tilted TM orientation allows LN01 to interact simultaneously with the peptidic component of the MPER epitope and membrane via two specific lipid binding sites of the antibody paratope. Although LN01 carries a high load of somatic mutations, most key residues interacting with the MPER epitope and lipids are germline encoded, lending support for the LN01 epitope as a candidate for lineage-based vaccine development.
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hal-02336304 , version 1 (19-12-2019)

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Dora Pinto, Craig Fenwick, Christophe Caillat, Chiara Silacci, Serafima Guseva, et al.. Structural Basis for Broad HIV-1 Neutralization by a Novel MPER-Specific Human Broadly Neutralizing Antibody. Cell Host and Microbe, 2019, 26 (5), pp.623-637.e8. ⟨10.2139/ssrn.3416843⟩. ⟨hal-02336304⟩
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