tailieunhanh - Báo cáo khoa học: Structures of human proteinase 3 and neutrophil elastase – so similar yet so different

Proteinase 3 and neutrophil elastase are serine proteinases of the polymor-phonuclear neutrophils, which are considered to have both similar localiza-tion and ligand specificity because of their high sequence similarity. However, recent studies indicate that they might have different and yet complementary physiologic roles. | REVIEW ARTICLE Structures of human proteinase 3 and neutrophil elastase - so similar yet so different Eric Hajjar1 Torben Broemstrup2 3 Chahrazade Kantari4 Véronique Witko-Sarsat4 5 and Nathalie Reuter3 6 1 Dipartimento di Fisica University of Cagliari CA Italy 2 Department of Informatics University of Bergen Norway 3 ComputationalBiology Unit BCCS University of Bergen Norway 4 Inserm U845 and U1016 Paris France 5 Institut Cochin Universite Paris Descartes CNRS UMR 8104 France 6 Department of Molecular Biology University of Bergen Norway Keywords human neutrophil elastase inflammation myeloblastin neutrophil proteinase 3 vasculitis Wegener granulomatosis Correspondence N. Reuter Department of Molecular Biology University of Bergen Thormohlensgt 55 N-5008 Bergen Norway Fax 47 555 84295 Tel 47 555 84040 E-mail Received 22 January 2010 revised 11 March 2010 accepted 18 March 2010 doi Proteinase 3 and neutrophil elastase are serine proteinases of the polymorphonuclear neutrophils which are considered to have both similar localization and ligand specificity because of their high sequence similarity. However recent studies indicate that they might have different and yet complementary physiologic roles. Specifically proteinase 3 has intracellular specific protein substrates resulting in its involvement in the regulation of intracellular functions such as proliferation or apoptosis. It behaves as a peripheral membrane protein and its membrane expression is a risk factor in chronic inflammatory diseases. Moreover in contrast to human neutrophil elastase proteinase 3 is the preferred target antigen in Wegener s granulomatosis a particular type of vasculitis. We review the structural basis for the different ligand specificities and membrane binding mechanisms of both enzymes as well as the putative anti-neutrophil cytoplasm autoantibody epitopes on human neutrophil elastase 3. We also address the differences existing