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

in: Cell Reports (2020)
Rujas, Edurne; Insausti, Sara; Leaman, Daniel P.; Carravilla, Pablo; González-Resines, Saul; Monceaux, Valérie; Sánchez-Eugenia, Rubén; García-Porras, Miguel; Iloro, Ibon; Zhang, Lei; Elortza, Félix; Julien, Jean-Philippe; Saéz-Cirión, Asier; Zwick, Michael B.; Eggeling, Christian; Ojida, Akio; Domene, C.; Caaveiro, Jose M. M.; Nieva, José L.
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 10E8as amodel, linear andpolycyclic synthetic aromatic compounds are introducedat selected sites. Molecular dynamics simulations predict the favorable interactions of these synthetic compounds with the viral lipidmembrane, where the epitope of the HIV-1 glycoprotein Env is located. Chemicalmodification of 10E8 with aromatic acetamides facilitates the productive and specific recognition of the native antigen, partially buriedin the crowdedenvironmentof the viralmembrane, resultingin adramatic 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.

Third party cookies & scripts

This site uses cookies. For optimal performance, smooth social media and promotional use, it is recommended that you agree to third party cookies and scripts. This may involve sharing information about your use of the third-party social media, advertising and analytics website.
For more information, see privacy policy and imprint.
Which cookies & scripts and the associated processing of your personal data do you agree with?

You can change your preferences anytime by visiting privacy policy.