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

Publication year: 2019
Authors: Ierich J.C.M. 1,2, Brum D.G. 3, Moraes A.S. 1,2, Higa A.M. 1,2, Garcia P.S. 1,2, Miyazaki C.M. 4, Ferreira M. 4, Peroni L.A. 5, Oliveira G.S. 6, Franca E.F. 6, Freitas L.C.G. 7, Leite F.L. 8
Affiliations:

1- Nanoneurobiophysics Research Group, Department of Physics, Chemistry and Mathematics, Federal University of São Carlos, Sorocaba, 18052-780, Brazil
2 - Institute of Tropical Medicine of São Paulo, University of São Paulo, São Paulo, 05403-000, Brazil
3 - Department of Neurology, Psychology and Psychiatry, UNESP - São Paulo State University, Botucatu, 18618-687, Brazil
4 - Science and Technology Centre for Sustainability, Federal University of São Carlos, Sorocaba, 18052-780, Brazil
5 - Rheabiotech Laboratory Research and Development, Campinas, 13084-791, Brazil
6 - Institute of Chemistry, Federal University of Uberlândia, Uberlândia, 38400-902, Brazil
7 - Department of Chemistry, Federal University of São Carlos, São Carlos, 13565-905, Brazil
8 - Nanoneurobiophysics Research Group, Department of Physics, Chemistry and Mathematics, Federal University of São Carlos, Sorocaba, 18052-780, Brazil

Published in: Scientific Reports, 2019, Vol. 9, Issue 1, p. 2033
doi: 10.1038/s41598-018-36578-8

Antigen-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 (ASP102, HIS103, SER104, TYR105, and GLN106), the well-known MOG92-106peptide 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 MOG92-106 and anti-MOG detachment, respectively. MOG92-106 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.


MP-SPR keywords: antibody-protein interaction, Au sensor slide, biosensing, cysteine, glycoprotein, in situ biosensor surface modification, protein A