PuSH - Publikationsserver des Helmholtz Zentrums München

Pang, Y.P.* ; Moura, M.C.* ; Thompson, G.E.* ; Nelson, D.R.* ; Hummel, A.M.* ; Jenne, D. ; Emerling, D.* ; Volkmuth, W.* ; Robinson, W.H.* ; Specks, U.*

Remote activation of a latent epitope in an autoantigen decoded with simulated B-factors.

Front. Immunol. 10:2467 (2019)
Verlagsversion Forschungsdaten DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
Mutants of a catalytically inactive variant of Proteinase 3 (PR3)-iPR3-Val(103) possessing a Ser195Ala mutation relative to wild-type PR3-Val(103)-offer insights into how autoantigen PR3 interacts with antineutrophil cytoplasmic antibodies (ANCAs) in granulomatosis with polyangiitis (GPA) and whether such interactions can be interrupted. Here we report that iHm5-Val(103), a triple mutant of iPR3-Val(103), bound a monoclonal antibody (moANCA518) from a GPA patient on an epitope remote from the mutation sites, whereas the corresponding epitope of iPR3-Val(103) was latent to moANCA518. Simulated B-factor analysis revealed that the binding of moANCA518 to iHm5-Val(103) was due to increased main-chain flexibility of the latent epitope caused by remote mutations, suggesting rigidification of epitopes with therapeutics to alter pathogenic PR3 center dot ANCA interactions as new GPA treatments.
Altmetric
Weitere Metriken?
Zusatzinfos bearbeiten [➜Einloggen]
Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Autoimmunity ; Autoantigen ; Antigenicity ; Antineutrophil Cytoplasmic Antibody ; Proteinase 3 ; B-factor; Antineutrophil Cytoplasmic Antibodies; Proteinase-3 Pr3; Wegeners-granulomatosis; Neutrophil Elastase; Molecular-dynamics; Capture-elisa; Recognition; Refinement; Interference; Restraints
ISSN (print) / ISBN 1664-3224
e-ISSN 1664-3224
Zeitschrift Frontiers in Immunology
Quellenangaben Band: 10, Heft: , Seiten: , Artikelnummer: 2467 Supplement: ,
Verlag Frontiers
Verlagsort Avenue Du Tribunal Federal 34, Lausanne, Ch-1015, Switzerland
Begutachtungsstatus