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

Edurne Rujas, Sara Insausti, Daniel P Leaman, Pablo Carravilla, Saul González-Resines, Valérie Monceaux, Rubén Sánchez-Eugenia, Miguel García-Porras, Ibon Iloro, Lei Zhang, Félix Elortza, Jean-Philippe Julien, Asier Saéz-Cirión, Michael B Zwick, Christian Eggeling, Akio Ojida, Carmen Domene, Jose M M Caaveiro, José L Nieva

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8 Citations (SciVal)


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.

Original languageEnglish
Article number108037
JournalCell Reports
Issue number7
Publication statusPublished - 18 Aug 2020

Bibliographical note

Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.


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