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Neutrophil myeloperoxidase harbors distinct site-specific peculiarities in its glycosylation.
Reiding, Karli R; Franc, Vojtech; Huitema, Minke G; Brouwer, Elisabeth; Heeringa, Peter; Heck, Albert J R.
Afiliação
  • Reiding KR; Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, University of Utrecht, 3584 CH Utrecht, The Netherlands k.r.reiding@uu.nl.
  • Franc V; Netherlands Proteomics Center, 3584 CH Utrecht, The Netherlands.
  • Huitema MG; Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, University of Utrecht, 3584 CH Utrecht, The Netherlands.
  • Brouwer E; Netherlands Proteomics Center, 3584 CH Utrecht, The Netherlands.
  • Heeringa P; Department of Rheumatology and Clinical Immunology, University Medical Center Groningen, University of Groningen, 9700 AB Groningen, The Netherlands.
  • Heck AJR; Department of Rheumatology and Clinical Immunology, University Medical Center Groningen, University of Groningen, 9700 AB Groningen, The Netherlands.
J Biol Chem ; 294(52): 20233-20245, 2019 12 27.
Article em En | MEDLINE | ID: mdl-31719144
Anti-neutrophil cytoplasmic autoantibodies (ANCAs) are directed against lysosomal components of neutrophils. ANCAs directed to proteinase 3 and myeloperoxidase (MPO) in particular are associated with distinct forms of small vessel vasculitides. MPO is an abundant neutrophil-derived heme protein that is part of the antimicrobial defense system. The protein is typically present in the azurophilic granules of neutrophils, but a large portion may also enter the extracellular space. It remains unclear why MPO is frequently the target of antibody-mediated autoimmune responses. MPO is a homodimeric glycoprotein, posttranslationally modified with complex sugars at specific sites. Glycosylation can strongly influence protein function, affecting its folding, receptor interaction, and backbone accessibility. MPO potentially can be heavily modified as it harbors 5 putative N-glycosylation sites (10 in the mature dimer). Although considered important for MPO structure and function, the full scope and relative abundance of the glycans attached to MPO is unknown. Here, combining bottom-up glycoproteomics and native MS approaches, we structurally characterized MPO from neutrophils of healthy human donors. We quantified the relative occupancy levels of the glycans at each of the five sites and observed complex heterogeneity and site-specific glycosylation. In particular, we detected glycosylation phenotypes uncommon for glycoproteins in the extracellular space, such as a high abundance of phosphorylated high-mannose species and severely truncated small glycans having the size of paucimannose or smaller. We hypothesize that the atypical glycosylation pattern found on MPO might contribute to its specific processing and presentation as a self-antigen by antigen-presenting cells.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Peroxidase / Neutrófilos Limite: Humans Idioma: En Ano de publicação: 2019 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Peroxidase / Neutrófilos Limite: Humans Idioma: En Ano de publicação: 2019 Tipo de documento: Article