Structural basis for the recognition in an idiotype-anti-idiotype antibody complex related to celiac disease

Handle URI:
http://hdl.handle.net/10754/334558
Title:
Structural basis for the recognition in an idiotype-anti-idiotype antibody complex related to celiac disease
Authors:
Vangone, Anna; Abdel-Azeim, Safwat ( 0000-0001-8611-1251 ) ; Caputo, Ivana; Sblattero, Daniele; Di Niro, Roberto; Cavallo, Luigi ( 0000-0002-1398-338X ) ; Oliva, Romina
Abstract:
Anti-idiotype antibodies have potential therapeutic applications in many fields, including autoimmune diseases. Herein we report the isolation and characterization of AIM2, an anti-idiotype antibody elicited in a mouse model upon expression of the celiac disease-specific autoantibody MB2.8 (directed against the main disease autoantigen type 2 transglutaminase, TG2). To characterize the interaction between the two antibodies, a 3D model of the MB2.8-AIM2 complex has been obtained by molecular docking. Analysis and selection of the different obtained docking solutions was based on the conservation within them of the inter-residue contacts. The selected model is very well representative of the different solutions found and its stability is confirmed by molecular dynamics simulations. Furthermore, the binding mode it adopts is very similar to that observed in most of the experimental structures available for idiotype-anti-idiotype antibody complexes. In the obtained model, AIM2 is directed against the MB2.8 CDR region, especially on its variable light chain. This makes the concurrent formation of the MB2.8-AIM2 complex and of the MB2.8-TG2 complex incompatible, thus explaining the experimentally observed inhibitory effect on the MB2.8 binding to TG2. © 2014 Vangone et al.
KAUST Department:
KAUST Catalysis Center (KCC)
Citation:
Vangone A, Abdel-Azeim S, Caputo I, Sblattero D, Di Niro R, et al. (2014) Structural Basis for the Recognition in an Idiotype-Anti-Idiotype Antibody Complex Related to Celiac Disease. PLoS ONE 9: e102839. doi:10.1371/journal.pone.0102839.
Publisher:
Public Library of Science (PLoS)
Journal:
PLoS ONE
Issue Date:
30-Jul-2014
DOI:
10.1371/journal.pone.0102839
PubMed ID:
25076134
PubMed Central ID:
PMC4116137
Type:
Article
ISSN:
19326203
Appears in Collections:
Articles; KAUST Catalysis Center (KCC)

Full metadata record

DC FieldValue Language
dc.contributor.authorVangone, Annaen
dc.contributor.authorAbdel-Azeim, Safwaten
dc.contributor.authorCaputo, Ivanaen
dc.contributor.authorSblattero, Danieleen
dc.contributor.authorDi Niro, Robertoen
dc.contributor.authorCavallo, Luigien
dc.contributor.authorOliva, Rominaen
dc.date.accessioned2014-11-11T14:29:35Z-
dc.date.available2014-11-11T14:29:35Z-
dc.date.issued2014-07-30en
dc.identifier.citationVangone A, Abdel-Azeim S, Caputo I, Sblattero D, Di Niro R, et al. (2014) Structural Basis for the Recognition in an Idiotype-Anti-Idiotype Antibody Complex Related to Celiac Disease. PLoS ONE 9: e102839. doi:10.1371/journal.pone.0102839.en
dc.identifier.issn19326203en
dc.identifier.pmid25076134en
dc.identifier.doi10.1371/journal.pone.0102839en
dc.identifier.urihttp://hdl.handle.net/10754/334558en
dc.description.abstractAnti-idiotype antibodies have potential therapeutic applications in many fields, including autoimmune diseases. Herein we report the isolation and characterization of AIM2, an anti-idiotype antibody elicited in a mouse model upon expression of the celiac disease-specific autoantibody MB2.8 (directed against the main disease autoantigen type 2 transglutaminase, TG2). To characterize the interaction between the two antibodies, a 3D model of the MB2.8-AIM2 complex has been obtained by molecular docking. Analysis and selection of the different obtained docking solutions was based on the conservation within them of the inter-residue contacts. The selected model is very well representative of the different solutions found and its stability is confirmed by molecular dynamics simulations. Furthermore, the binding mode it adopts is very similar to that observed in most of the experimental structures available for idiotype-anti-idiotype antibody complexes. In the obtained model, AIM2 is directed against the MB2.8 CDR region, especially on its variable light chain. This makes the concurrent formation of the MB2.8-AIM2 complex and of the MB2.8-TG2 complex incompatible, thus explaining the experimentally observed inhibitory effect on the MB2.8 binding to TG2. © 2014 Vangone et al.en
dc.language.isoenen
dc.publisherPublic Library of Science (PLoS)en
dc.rightsThis is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en
dc.rightsArchived with thanks to PLoS ONEen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.titleStructural basis for the recognition in an idiotype-anti-idiotype antibody complex related to celiac diseaseen
dc.typeArticleen
dc.contributor.departmentKAUST Catalysis Center (KCC)en
dc.identifier.journalPLoS ONEen
dc.identifier.pmcidPMC4116137en
dc.eprint.versionPublisher's Version/PDFen
dc.contributor.institutionDepartment of Chemistry and Biology, University of Salerno, Fisciano, Salerno, Italyen
dc.contributor.institutionEuropean Laboratory for the Investigation of Food-Induced Diseases (ELFID), University Federico II, Naples, Italyen
dc.contributor.institutionDepartment of Health Sciences, Interdisciplinary Research Center of Autoimmune Diseases (IRCAD), University of Eastern Piedmont, Novara, Italyen
dc.contributor.institutionDepartment of Immunology, University of Pittsburgh, Pittsburgh, PA, United Statesen
dc.contributor.institutionDepartment of Sciences and Technologies, University Parthenope of Naples, Naples, Italyen
dc.contributor.institutionBijvoet Center for Biomolecular Research, Utrecht University, Utrecht, Netherlandsen
dc.contributor.affiliationKing Abdullah University of Science and Technology (KAUST)en
kaust.authorAbdel-Azeim, Safwaten
kaust.authorCavallo, Luigien

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