Pinto, Dora Fenwick, Craig Caillat, Christophe Silacci, Chiara Guseva, Serafima Dehez, François Chipot, Christophe Barbieri, Sonia Minola, Andrea Jarrossay, David Tomaras, Georgia D. Shen, Xiaoying Riva, Agostino Tarkowski, Maciej Schwartz, Olivier Bruel, Timothée Dufloo, Jérémy Seaman, Michael S. Montefiori, David C. Lanzavecchia, Antonio Corti, Davide Pantaleo, Giuseppe Weissenhorn, Winfried 2019-11-13 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. application/pdf https://susi.usi.ch/global/documents/319183 https://localhost:5000/ark:/12658/srd1319183 https://susi.usi.ch/documents/319183/files/Pinto_chm_2019.pdf eng info:eu-repo/semantics/altIdentifier/doi/10.1016/j.chom.2019.09.016 info:eu-repo/semantics/altIdentifier/ark/12658/srd1319183 info:eu-repo/semantics/openAccess CC BY Cell host & microbe. - 2019, vol. 26, no. 5, p. p. 623-637.e8 HIV-1 Env gp41 MPER Broadly neutralizing antibody LN01 4E10 10E8 Membrane interaction info:eu-repo/classification/udc/57/59 Structural basis for broad HIV-1 neutralization by the MPER-specific human broadly neutralizing antibody LN01 http://purl.org/coar/resource_type/c_6501