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

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

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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Autores:	Rujas, Edurne, Insausti, Sara, Leaman, Daniel P., Carravilla, Pablo, González-Resines, Saúl, Monceaux, Valérie, Sánchez-Eugenia, Rubén, García-Porras, Miguel, Iloro, Ibon, Zhang, Lei, Elortza, Félix, Julien, Jean-Philippe, Sáez-Cirión, Asier, Zwick, Michael B., Eggeling, Christian, Ojida, Akio, Domene, Carmen, Caaveiro, José M. M., Nieva, José Luis
Tipo de recurso:	artículo
Estado:	Versión publicada
Fecha de publicación:	2020
País:	España
Institución:	Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:	DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:	oai:digital.csic.es:10261/336847
Acceso en línea:	http://hdl.handle.net/10261/336847 https://api.elsevier.com/content/abstract/scopus_id/85089410885
Access Level:	acceso abierto
Palabra clave:	HIV-1 antibody Antibody engineering Antibody-membrane interaction Aromatic grafting Membrane biophysics Protein-membrane interaction Site-selective chemical modification

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oai_identifier_str	oai:digital.csic.es:10261/336847
network_acronym_str	ES
network_name_str	España
repository_id_str
dc.title.none.fl_str_mv	Affinity for the Interface Underpins Potency of Antibodies Operating In Membrane Environments
title	Affinity for the Interface Underpins Potency of Antibodies Operating In Membrane Environments
spellingShingle	Affinity for the Interface Underpins Potency of Antibodies Operating In Membrane Environments Rujas, Edurne HIV-1 antibody Antibody engineering Antibody-membrane interaction Aromatic grafting Membrane biophysics Protein-membrane interaction Site-selective chemical modification
title_short	Affinity for the Interface Underpins Potency of Antibodies Operating In Membrane Environments
title_full	Affinity for the Interface Underpins Potency of Antibodies Operating In Membrane Environments
title_fullStr	Affinity for the Interface Underpins Potency of Antibodies Operating In Membrane Environments
title_full_unstemmed	Affinity for the Interface Underpins Potency of Antibodies Operating In Membrane Environments
title_sort	Affinity for the Interface Underpins Potency of Antibodies Operating In Membrane Environments
dc.creator.none.fl_str_mv	Rujas, Edurne Insausti, Sara Leaman, Daniel P. Carravilla, Pablo González-Resines, Saúl Monceaux, Valérie Sánchez-Eugenia, Rubén García-Porras, Miguel Iloro, Ibon Zhang, Lei Elortza, Félix Julien, Jean-Philippe Sáez-Cirión, Asier Zwick, Michael B. Eggeling, Christian Ojida, Akio Domene, Carmen Caaveiro, José M. M. Nieva, José Luis
author	Rujas, Edurne
author_facet	Rujas, Edurne Insausti, Sara Leaman, Daniel P. Carravilla, Pablo González-Resines, Saúl Monceaux, Valérie Sánchez-Eugenia, Rubén García-Porras, Miguel Iloro, Ibon Zhang, Lei Elortza, Félix Julien, Jean-Philippe Sáez-Cirión, Asier Zwick, Michael B. Eggeling, Christian Ojida, Akio Domene, Carmen Caaveiro, José M. M. Nieva, José Luis
author_role	author
author2	Insausti, Sara Leaman, Daniel P. Carravilla, Pablo González-Resines, Saúl Monceaux, Valérie Sánchez-Eugenia, Rubén García-Porras, Miguel Iloro, Ibon Zhang, Lei Elortza, Félix Julien, Jean-Philippe Sáez-Cirión, Asier Zwick, Michael B. Eggeling, Christian Ojida, Akio Domene, Carmen Caaveiro, José M. M. Nieva, José Luis
author2_role	author author author author author author author author author author author author author author author author author author
dc.contributor.none.fl_str_mv	Eusko Jaurlaritza Universidad del País Vasco European Commission National Institutes of Health (US) James B. Pendleton Charitable Trust Japan Society for the Promotion of Science Ministerio de Economía y Competitividad (España) Ministerio de Ciencia, Innovación y Universidades (España) Agencia Estatal de Investigación (España) Medical Research Council (UK) German Research Foundation Wolfson Foundation Wellcome Trust Azrieli Foundation Canada Research Chairs Japan Agency for Medical Research and Development Carravilla, Pablo [0000-0001-6592-7630] Sáez-Cirión, Asier [0000-0003-2406-7536] Eggeling, Christian [0000-0002-3698-5599] Caaveiro, José M. M. [0000-0001-5568-2369] Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv	HIV-1 antibody Antibody engineering Antibody-membrane interaction Aromatic grafting Membrane biophysics Protein-membrane interaction Site-selective chemical modification
topic	HIV-1 antibody Antibody engineering Antibody-membrane interaction Aromatic grafting Membrane biophysics Protein-membrane interaction Site-selective chemical modification
description	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.
publishDate	2020
dc.date.none.fl_str_mv	2020 2023 2023
dc.type.none.fl_str_mv	info:eu-repo/semantics/article http://purl.org/coar/resource_type/c_6501 Publisher's version info:eu-repo/semantics/publishedVersion
format	article
status_str	publishedVersion
dc.identifier.none.fl_str_mv	http://hdl.handle.net/10261/336847 https://api.elsevier.com/content/abstract/scopus_id/85089410885
url	http://hdl.handle.net/10261/336847 https://api.elsevier.com/content/abstract/scopus_id/85089410885
dc.language.none.fl_str_mv	Inglés
language_invalid_str_mv	Inglés
dc.relation.none.fl_str_mv	#PLACEHOLDER_PARENT_METADATA_VALUE# #PLACEHOLDER_PARENT_METADATA_VALUE# #PLACEHOLDER_PARENT_METADATA_VALUE# info:eu-repo/grantAgreement/EC/H2020/790012 info:eu-repo/grantAgreement/MINECO//BIO2015-64421-R info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/RTI2018-095624-B-C21 https://doi.org/10.1016/j.celrep.2020.108037 Sí
dc.rights.none.fl_str_mv	info:eu-repo/semantics/openAccess
eu_rights_str_mv	openAccess
dc.format.none.fl_str_mv	application/pdf
dc.publisher.none.fl_str_mv	Cell Press
publisher.none.fl_str_mv	Cell Press
dc.source.none.fl_str_mv	reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str	Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str	DIGITAL.CSIC. Repositorio Institucional del CSIC
collection	DIGITAL.CSIC. Repositorio Institucional del CSIC
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spelling	Affinity for the Interface Underpins Potency of Antibodies Operating In Membrane EnvironmentsRujas, EdurneInsausti, SaraLeaman, Daniel P.Carravilla, PabloGonzález-Resines, SaúlMonceaux, ValérieSánchez-Eugenia, RubénGarcía-Porras, MiguelIloro, IbonZhang, LeiElortza, FélixJulien, Jean-PhilippeSáez-Cirión, AsierZwick, Michael B.Eggeling, ChristianOjida, AkioDomene, CarmenCaaveiro, José M. M.Nieva, José LuisHIV-1 antibodyAntibody engineeringAntibody-membrane interactionAromatic graftingMembrane biophysicsProtein-membrane interactionSite-selective chemical modificationThe 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.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 H2020-MSCA-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 (BIO2015-64421-R and MINECO/AEI/FEDER, UE to J.L.N.); Spanish MCIU (RTI2018-095624-B-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).Peer reviewedCell PressEusko JaurlaritzaUniversidad del País VascoEuropean CommissionNational Institutes of Health (US)James B. Pendleton Charitable TrustJapan Society for the Promotion of ScienceMinisterio de Economía y Competitividad (España)Ministerio de Ciencia, Innovación y Universidades (España)Agencia Estatal de Investigación (España)Medical Research Council (UK)German Research FoundationWolfson FoundationWellcome TrustAzrieli FoundationCanada Research ChairsJapan Agency for Medical Research and DevelopmentCarravilla, Pablo [0000-0001-6592-7630]Sáez-Cirión, Asier [0000-0003-2406-7536]Eggeling, Christian [0000-0002-3698-5599]Caaveiro, José M. M. [0000-0001-5568-2369]Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]202320232020info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionapplication/pdfhttp://hdl.handle.net/10261/336847https://api.elsevier.com/content/abstract/scopus_id/85089410885reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/EC/H2020/790012info:eu-repo/grantAgreement/MINECO//BIO2015-64421-Rinfo:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/RTI2018-095624-B-C21https://doi.org/10.1016/j.celrep.2020.108037Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/3368472026-05-22T06:33:51Z
score	15.811543

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

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