title: What you should know about PR3-ANCA. Conformational requirements of proteinase 3 (PR3) for enzymatic activity and recognition by PR3-ANCA.
abstract: The neutrophil azurophil granule constituent proteinase 3 (PR3) is the principal antigen for anti-neutrophil cytoplasmic antibodies (ANCA) in Wegener's granulomatosis. The conformation of the mature PR3 enzyme results from intracellular post-translational processing. The nascent molecule undergoes proteolytic cleavage of the amino-terminal signal peptide and activation dipeptide and of a carboxy-terminal peptide extension. The conformation of PR3 is stabilized by four disulfide bonds and, to a lesser extent, by asparagine-linked glycosylation. Most anti-neutrophil cytoplasmic antibodies directed against proteinase 3 (PR3-ANCA) recognize conformational epitopes. The expression of recombinant PR3 has provided a better understanding of the significance of the various intracellular processing steps for enzymatic activity and recognition by PR3-ANCA.
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Mayo Clinic and Foundation, Rochester, Minnesota 55905, USA. specks.ulrich@mayo.edu
authors.forename: U
authors.initials: U
authors.lastname: Specks
mesh_terms: D000818:Animals; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000276:immunology*; D000939:Epitopes / Q000276:immunology / Q000378:metabolism; D006801:Humans; D053146:Myeloblastin; D017434:Protein Structure, Tertiary / Q000502:physiology; D011994:Recombinant Proteins / Q000276:immunology* / Q000378:metabolism; D012697:Serine Endopeptidases / Q000276:immunology* / Q000378:metabolism
chemical_list: D019268:Antibodies, Antineutrophil Cytoplasmic; D000939:Epitopes; D011994:Recombinant Proteins; D012697:Serine Endopeptidases; D053146:Myeloblastin