Antibody-mediated biorecognition of myelin oligodendrocyte glycoprotein: computational evidence of demyelination-related epitopes

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dc.contributor.authorIerich, Jéssica Cristiane Magalhães
dc.contributor.authorBrum, Doralina Guimarães [UNESP]
dc.contributor.authorMoraes, Ariana de Souza
dc.contributor.authorHiga, Akemi Martins
dc.contributor.authorGarcia, Pâmela Soto
dc.contributor.authorMiyazaki, Celina Massumi
dc.contributor.authorFerreira, Marystela
dc.contributor.authorPeroni, Luís Antonio
dc.contributor.authorOliveira, Guedmiller Souza de
dc.contributor.authorFranca, Eduardo de Faria
dc.contributor.authorFreitas, Luiz Carlos Gomide
dc.contributor.authorLeite, Fabio Lima
dc.contributor.institutionUniversidade Federal de São Carlos (UFSCar)
dc.contributor.institutionUniversidade de São Paulo (USP)
dc.contributor.institutionUniversidade Estadual Paulista (Unesp)
dc.contributor.institutionRheabiotech Laboratory Research and Development
dc.contributor.institutionUniversidade Federal de Uberlândia (UFU)
dc.date.accessioned2019-10-06T16:17:22Z
dc.date.available2019-10-06T16:17:22Z
dc.date.issued2019-12-01
dc.description.abstractAntigen-antibody interaction is crucial in autoimmune disease pathogenesis, as multiple sclerosis and neuromyelitis optica. Given that, autoantibodies are essential biomolecules, of which the myelin oligodendrocyte glycoprotein (MOG) can figure as a target. Here we combined Molecular Dynamics (MD), Steered Molecular Dynamics (SMD), and Atomic Force Microscope (AFM) to detail MOG recognition by its specific antibody. The complex model consisted of the MOG external domain interacting with an experimental anti-MOG antibody from the Protein Data Bank (1PKQ). Computational data demonstrated thirteen MOG residues with a robust contribution to the antigen-antibody interaction. Comprising five of the thirteen anchor residues (ASP 102 , HIS 103 , SER 104 , TYR 105 , and GLN 106 ), the well-known MOG 92–106 peptide in complex with the anti-MOG was analysed by AFM and SMD. These analyses evidenced similar force values of 780 pN and 765 pN for computational and experimental MOG 92–106 and anti-MOG detachment, respectively. MOG 92–106 was responsible for 75% of the total force measured between MOG external domain and anti-MOG, holding the interaction with the antibody. The antigen-antibody binding was confirmed by Surface Plasmon Resonance (SPR) measurements. Combined approaches presented here can conveniently be adjusted to detail novel molecules in diseases research. This can optimize pre-clinical steps, guiding experiments, reducing costs, and animal model usage.en
dc.description.affiliationNanoneurobiophysics Research Group Department of Physics Chemistry and Mathematics Federal University of São Carlos
dc.description.affiliationInstitute of Tropical Medicine of São Paulo University of São Paulo
dc.description.affiliationDepartment of Neurology Psychology and Psychiatry UNESP - São Paulo State University
dc.description.affiliationScience and Technology Centre for Sustainability Federal University of São Carlos
dc.description.affiliationRheabiotech Laboratory Research and Development
dc.description.affiliationInstitute of Chemistry Federal University of Uberlândia
dc.description.affiliationDepartment of Chemistry Federal University of São Carlos
dc.description.affiliationUnespDepartment of Neurology Psychology and Psychiatry UNESP - São Paulo State University
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.description.sponsorshipIdFAPESP: 2012/50839-4
dc.description.sponsorshipIdFAPESP: 2013/09746-5
dc.description.sponsorshipIdFAPESP: 2014/12082-4
dc.description.sponsorshipIdFAPESP: 2014/15093-7
dc.description.sponsorshipIdFAPESP: 2014/21530-0
dc.description.sponsorshipIdFAPESP: 2014/26369-3
dc.description.sponsorshipIdFAPESP: 2015/05283-6
dc.description.sponsorshipIdFAPESP: 2015/06847-0
dc.description.sponsorshipIdFAPESP: 2016/19387-0
dc.description.sponsorshipIdCNPq: 305069/2016-0
dc.description.sponsorshipIdCNPq: 459768/2014-0
dc.identifierhttp://dx.doi.org/10.1038/s41598-018-36578-8
dc.identifier.citationScientific Reports, v. 9, n. 1, 2019.
dc.identifier.doi10.1038/s41598-018-36578-8
dc.identifier.issn2045-2322
dc.identifier.scopus2-s2.0-85061565923
dc.identifier.urihttp://hdl.handle.net/11449/188729
dc.language.isoeng
dc.relation.ispartofScientific Reports
dc.rights.accessRightsAcesso aberto
dc.sourceScopus
dc.titleAntibody-mediated biorecognition of myelin oligodendrocyte glycoprotein: computational evidence of demyelination-related epitopesen
dc.typeArtigo
unesp.author.orcid0000-0002-7447-9566[1]
unesp.author.orcid0000-0001-7453-0133[3]
unesp.author.orcid0000-0002-9459-8167[7]
unesp.author.orcid0000-0001-7441-4263[9]

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