Affinity for the Interface Underpins Potency of Antibodies Operating In Membrane Environments

The contribution of membrane interfacial interactions to recognition of membrane-embedded antigens by antibodies is currently unclear. This report demonstrates the optimization of this type of antibodies via chemical modification of regions near the membrane but not directly involved in the recognit...

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Detalles Bibliográficos
Autores: Rujas Díez, Edurne, Insausti González, Sara, Leaman, Daniel P., Carravilla Palomanes, Pablo, González Resines, Saul, Monceaux, Valérie, Sánchez Eugenia, Rubén, García Porras, Miguel, Iloro, Ibon, Zhang, Lei, Elortza, Felix, Julien, Jean-Philippe, Sáez Cirión, Asier, Zwick, Michael B., Eggeling, Christian, Ojida, Akio, Domene, Carmen, Caaveiro, Jose M.M., Nieva Escandón, José Luis
Tipo de recurso: artículo
Fecha de publicación:2020
País:España
Institución:Universidad del País Vasco
Repositorio:Addi. Archivo Digital para la Docencia y la Investigación
OAI Identifier:oai:addi.ehu.eus:10810/49145
Acceso en línea:http://hdl.handle.net/10810/49145
Access Level:acceso abierto
Palabra clave:immunodeficiency-virus type-1
molecular-dynamics simulation
monoclonal-antibody
perfringolysin-o
epitope
neutralization
hiv-1
protein
assay
identification
Descripción
Sumario:The contribution of membrane interfacial interactions to recognition of membrane-embedded antigens by antibodies is currently unclear. This report demonstrates the optimization of this type of antibodies via chemical modification of regions near the membrane but not directly involved in the recognition of the epitope. Using the HIV-1 antibody 10E8 as a model, linear and polycyclic synthetic aromatic compounds are introduced at selected sites. Molecular dynamics simulations predict the favorable interactions of these synthetic compounds with the viral lipid membrane, where the epitope of the HIV-1 glycoprotein Env is located. Chemical modification of 10E8 with aromatic acetamides facilitates the productive and specific recognition of the native antigen, partially buried in the crowded environment of the viral membrane, resulting in a dramatic increase of its capacity to block viral infection. These observations support the harnessing of interfacial affinity through site-selective chemical modification to optimize the function of antibodies that target membrane-proximal epitopes.

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