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dc.contributor.authorRujas Díez, Edurne
dc.contributor.authorInsausti González, Sara
dc.contributor.authorLeaman, Daniel P.
dc.contributor.authorCarravilla Palomanes, Pablo ORCID
dc.contributor.authorGonzález Resines, Saul
dc.contributor.authorMonceaux, Valérie
dc.contributor.authorSánchez Eugenia, Rubén ORCID
dc.contributor.authorGarcía Porras, Miguel
dc.contributor.authorIloro, Ibon
dc.contributor.authorZhang, Lei
dc.contributor.authorElortza, Felix
dc.contributor.authorJulien, Jean Philippe
dc.contributor.authorSáez Cirión, Asier
dc.contributor.authorZwick, Michael B.
dc.contributor.authorEggeling, Christian
dc.contributor.authorOjida, Akio
dc.contributor.authorDomene, Carmen
dc.contributor.authorCaaveiro, Jose M.M.
dc.contributor.authorNieva Escandón, José Luis
dc.identifier.citationCell Reports 32(7) : (2020) // Article ID 108037es_ES
dc.description.abstractThe 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.es_ES
dc.description.sponsorshipWe are grateful to Professor Ueda (Kyushu University) for valuable advice. C.D. acknowledges RES (Red Espanola de Supercomputacio ' n) for providing computational resources. S.I. received a pre-doctoral fellowship from the Basque Government. P.C. acknowledges a research associate contract from the University of the Basque Country (DOCREC18/01) and a postdoctoral fellowship from the Basque Government (POS_2018_1_0066).This study was supported by the following grants: European Commission (790012 SI H2020MSCA-IF-2017 to E.R., J.-P.J., and J.L.N.); US NIAID (NIH) (R01 AI143563 to M.B.Z.); James B. Pendleton Charitable Trust (to M.B.Z.); Grant-in-Aid for Scientific Research on Innovative Areas "Chemistry for Multimolecular Crowding Biosystems, JSPS KAKENHI (JP17H06349 to A.O.); JSPS KAKENHI (15K06962 and 20H03228 to J.M.M.C.); Spanish MINECO (BIO2015-64421R and MINECO/AEI/FEDER, UE to J.L.N.); Spanish MCIU (RTI2018-095624B-C21 and MCIU/AEI/FEDER, UE to J.L.N.); and the Basque Government (IT1196-19) (to J.L.N.). C.E. acknowledges funding from Medical Research Council (MC_UU_12010/unit programs G0902418 and MC_UU_12025), Wolfson Foundation, Deutsche Forschungsgemeinschaft (Research unit 1905, Excellence Cluster Balance of the Microverse, Collaborative Research Centre 1278 Polytarget), Wellcome Institutional Strategic Support Fund, Oxford internal funds (EPA Cephalosporin Fund and John Fell Fund), and support from the Micron Oxford Advanced Bioimaging Unit (Wellcome Trust funding 107457/Z/15/Z). This research was undertaken, in part, thanks to funding from the CIFAR Azrieli Global Scholar program (to J.-P.J.) and the Canada Research Chairs program (950-231604 to J.-P.J.). This work was also supported by the Platform Project for Supporting Drug Discovery and Life Science Research (Basis for Supporting Innovative Drug Discovery and Life Science Research [BINDS] from AMED JP19am0101091).es_ES
dc.publisherCell Presses_ES
dc.subjectimmunodeficiency-virus type-1es_ES
dc.subjectmolecular-dynamics simulationes_ES
dc.titleAffinity for the Interface Underpins Potency of Antibodies Operating In Membrane Environmentses_ES
dc.rights.holder2020 The Author(s). This is an open access article under the CC BY-NC-ND license (
dc.rights.holderAtribución-NoComercial-SinDerivadas 3.0 España*
dc.departamentoesBioquímica y biología moleculares_ES
dc.departamentoeuBiokimika eta biologia molekularraes_ES

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2020 The Author(s). This is an open access article under the CC BY-NC-ND license (
Except where otherwise noted, this item's license is described as 2020 The Author(s). This is an open access article under the CC BY-NC-ND license (