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 Iturbe, Johana, De la Arada Echevarría, Igor, Partida Hanon, Angélica, Rujas Díez, Edurne, Arribas, Madalen, Insausti González, Sara, Valotteau, Claire, Valle García, Javier, Andreu, David, Caaveiro, Jose M.M., Jiménez, María Ángeles, Apellaniz Unzalu, Beatriz, Redondo Morata, Lorena, Nieva Escandón, José Luis
Formato: artículo
Fecha de publicación:2022
País:España
Recursos:Universidad del País Vasco
Repositorio:Addi. Archivo Digital para la Docencia y la Investigación
OAI Identifier:oai:addi.ehu.eus:10810/58493
Acesso em linha:http://hdl.handle.net/10810/58493
Access Level:acceso abierto
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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