Torralba, JohanaArada, Igor de laPartida-Hanon, AngélicaRujas, EdurneArribas, MadalenInsausti, SaraValotteau, ClaireValle, JavierAndreu Martínez, DavidCaaveiro, José M. M.Jiménez, María ÁngelesApellániz, BeatrizRedondo-Morata, LorenaNieva, José L.2022-12-152022-12-152022Torralba J, de la Arada I, Partida-Hanon A, Rujas E, Arribas M, Insausti S, Valotteau C, Valle J, Andreu D, Caaveiro JMM, Jiménez MA, Apellániz B, Redondo-Morata L, Nieva JL. Molecular recognition of a membrane-anchored HIV-1 pan-neutralizing epitope. Commun Biol. 2022 Nov 18;5(1):1265. DOI: 10.1038/s42003-022-04219-62399-3642http://hdl.handle.net/10230/55144Antibodies 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.application/pdfeng© The Author(s) 2022. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.info:eu-repo/semantics/articlehttp://dx.doi.org/10.1038/s42003-022-04219-6ImmunologyMembrane biophysicsNanoscale biophysicsinfo:eu-repo/semantics/openAccess