Title
Molecular recognition of a membrane-anchored HIV-1 pan-neutralizing epitope
Author
Johana Torralba, Igor de la Arada, Angélica Partida-Hanon, Edurne Rujas, Madalen Arribas, Sara Insausti, Claire Valotteau, Javier Valle, David Andreu, José M. M. Caaveiro, María Angeles Jiménez, Beatriz Apellániz, Lorena Redondo-Morata & José L. Nieva
Year
2022
Journal
Communications Biology
Abstract
Antibodies against the carboxy-terminal section of the membrane-proximal external region (C-MPER) of the HIV-1 envelope glycoprotein (Env) are considered as nearly pan-neutralizing. Development of vaccines capable of producing analogous broadly neutralizing antibodies requires deep understanding of the mechanism that underlies C-MPER recognition in membranes. Here, we use the archetypic 10E8 antibody and a variety of biophysical techniques including single-molecule approaches to study the molecular recognition of C-MPER in membrane mimetics. In contrast to the assumption that an interfacial MPER helix embodies the entire C-MPER epitope recognized by 10E8, our data indicate that transmembrane domain (TMD) residues contribute to binding affinity and specificity. Moreover, anchoring to membrane the helical C-MPER epitope through the TMD augments antibody binding affinity and relieves the effects exerted by the interfacial MPER helix on the mechanical stability of the lipid bilayer. These observations support that addition of TMD residues may result in more efficient and stable anti-MPER vaccines.
Full Article
Instrument
J-810
Keywords
antibodies, vaccine, TMD,