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Structural Basis for Broad HIV-1 Neutralization by the MPER-Specific Human Broadly Neutralizing Antibody LN01.

Publication ,  Journal Article
Pinto, D; Fenwick, C; Caillat, C; Silacci, C; Guseva, S; Dehez, F; Chipot, C; Barbieri, S; Minola, A; Jarrossay, D; Tomaras, GD; Shen, X ...
Published in: Cell Host Microbe
November 13, 2019

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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Published In

Cell Host Microbe

DOI

EISSN

1934-6069

Publication Date

November 13, 2019

Volume

26

Issue

5

Start / End Page

623 / 637.e8

Location

United States

Related Subject Headings

  • Protein Domains
  • Mice, Transgenic
  • Mice
  • Immunology
  • Humans
  • HIV-1
  • HIV Envelope Protein gp41
  • HIV Antibodies
  • HEK293 Cells
  • Female
 

Citation

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MLA
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Pinto, D., Fenwick, C., Caillat, C., Silacci, C., Guseva, S., Dehez, F., … Weissenhorn, W. (2019). Structural Basis for Broad HIV-1 Neutralization by the MPER-Specific Human Broadly Neutralizing Antibody LN01. Cell Host Microbe, 26(5), 623-637.e8. https://doi.org/10.1016/j.chom.2019.09.016
Pinto, Dora, Craig Fenwick, Christophe Caillat, Chiara Silacci, Serafima Guseva, François Dehez, Christophe Chipot, et al. “Structural Basis for Broad HIV-1 Neutralization by the MPER-Specific Human Broadly Neutralizing Antibody LN01.Cell Host Microbe 26, no. 5 (November 13, 2019): 623-637.e8. https://doi.org/10.1016/j.chom.2019.09.016.
Pinto D, Fenwick C, Caillat C, Silacci C, Guseva S, Dehez F, et al. Structural Basis for Broad HIV-1 Neutralization by the MPER-Specific Human Broadly Neutralizing Antibody LN01. Cell Host Microbe. 2019 Nov 13;26(5):623-637.e8.
Pinto, Dora, et al. “Structural Basis for Broad HIV-1 Neutralization by the MPER-Specific Human Broadly Neutralizing Antibody LN01.Cell Host Microbe, vol. 26, no. 5, Nov. 2019, pp. 623-637.e8. Pubmed, doi:10.1016/j.chom.2019.09.016.
Pinto D, Fenwick C, Caillat C, Silacci C, Guseva S, Dehez F, Chipot C, Barbieri S, Minola A, Jarrossay D, Tomaras GD, Shen X, Riva A, Tarkowski M, Schwartz O, Bruel T, Dufloo J, Seaman MS, Montefiori DC, Lanzavecchia A, Corti D, Pantaleo G, Weissenhorn W. Structural Basis for Broad HIV-1 Neutralization by the MPER-Specific Human Broadly Neutralizing Antibody LN01. Cell Host Microbe. 2019 Nov 13;26(5):623-637.e8.
Journal cover image

Published In

Cell Host Microbe

DOI

EISSN

1934-6069

Publication Date

November 13, 2019

Volume

26

Issue

5

Start / End Page

623 / 637.e8

Location

United States

Related Subject Headings

  • Protein Domains
  • Mice, Transgenic
  • Mice
  • Immunology
  • Humans
  • HIV-1
  • HIV Envelope Protein gp41
  • HIV Antibodies
  • HEK293 Cells
  • Female