Structural basis for broad neutralization of HIV-1 through the molecular recognition of 10E8 helical epitope at the membrane interface.

Edurne Rujas, Jose M.M. Caaveiro, Angelica Partida-Hanon, Naveed Gulzar, Koldo Morante, Beatriz Apellaniz, Miguel García-Porras, Marta Bruix, Kouhei Tsumoto, Jamie K. Scott, Maria Angeles Jimenez, José L. Nieva

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19 Citations (Scopus)

Abstract

The mechanism by which the HIV-1 MPER epitope is recognized by the potent neutralizing antibody 10E8 at membrane interfaces remains poorly understood. To solve this problem, we have optimized a 10E8 peptide epitope and analyzed the structure and binding activities of the antibody in membrane and membrane-like environments. The X-ray crystal structure of the Fab-peptide complex in detergents revealed for the rst time that the epitope of 10E8 comprises a continuous helix spanning the gp41 MPER/transmembrane domain junction (MPER-N-TMD; Env residues 671–687). The MPER-N-TMD
helix projects beyond the tip of the heavy-chain complementarity determining region 3 loop, indicating that the antibody sits parallel to the plane of the membrane in binding the native epitope. Biophysical, biochemical and mutational analyses demonstrated that strengthening the a nity of 10E8 for the TMD helix in a membrane environment, correlated with its neutralizing potency. Our research clari es the molecular mechanisms underlying broad neutralization of HIV-1 by 10E8, and the structure of its natural epitope. The conclusions of our research will guide future vaccine-design strategies targeting MPER.
Original languageEnglish
Article number38177
Number of pages13
JournalScientific Reports
Volume6
DOIs
Publication statusPublished - 2016

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    Rujas, E., Caaveiro, J. M. M., Partida-Hanon, A., Gulzar, N., Morante, K., Apellaniz, B., García-Porras, M., Bruix, M., Tsumoto, K., Scott, J. K., Jimenez, M. A., & Nieva, J. L. (2016). Structural basis for broad neutralization of HIV-1 through the molecular recognition of 10E8 helical epitope at the membrane interface. Scientific Reports, 6, [38177]. https://doi.org/10.1038/srep38177