Molecular recognition of a membrane-anchored HIV-1 pan-neutralizing epitope

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...

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Detalhes bibliográficos
Autores: Torralba, Johana, Arada, Igor de la, Partida-Hanon, Angélica, Rujas, Edurne, Arribas, Madalen, Insausti, Sara, Valotteau, Claire, Valle, Javier, Andreu Martínez, David, Caaveiro, José M. M., Jiménez, María Ángeles, Apellániz, Beatriz, Redondo-Morata, Lorena, Nieva, José L.
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2022
País:España
Recursos:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:10230/55144
Acesso em linha:http://hdl.handle.net/10230/55144
http://dx.doi.org/10.1038/s42003-022-04219-6
Access Level:acceso abierto
Palavra-chave:Immunology
Membrane biophysics
Nanoscale biophysics
Descrição
Resumo: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.

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