title: Proprotein Convertase Processing Enhances Peroxidasin Activity to Reinforce Collagen IV.
abstract: The basement membrane (BM) is a form of extracellular matrix that underlies cell layers in nearly all animal tissues. Type IV collagen, a major constituent of BMs, is critical for tissue development and architecture. The enzyme peroxidasin (Pxdn), an extracellular matrix-associated protein, catalyzes the formation of structurally reinforcing sulfilimine cross-links within the collagen IV network, an event essential to basement membrane integrity. Although the catalytic function of Pxdn is known, the regulation of its activity remains unclear. In this work we show through N-terminal sequencing, pharmacologic studies, and mutational analysis that proprotein convertases (PCs) proteolytically process human Pxdn at Arg-1336, a location relatively close to its C terminus. PC processing enhances the enzymatic activity of Pxdn and facilitates the formation of sulfilimine cross-links in collagen IV. Thus, PC processing of Pxdn is a key regulatory step that contributes to its function and, therefore, supports BM integrity and homeostasis.
authors.affiliation: From the Division of Nephrology and Hypertension, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee 37232.|the Department of Biological Sciences, Tennessee State University, Nashville, Tennessee 37209.|the Vanderbilt Center for Kidney Disease, Vanderbilt University Medical Center, Nashville, Tennessee 37232, and.
authors.forename: Selene
authors.initials: S
authors.lastname: Colon
authors.affiliation: From the Division of Nephrology and Hypertension, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee 37232, gautam.bhave@vanderbilt.edu.|the Vanderbilt Center for Kidney Disease, Vanderbilt University Medical Center, Nashville, Tennessee 37232, and.|the Department of Cell and Developmental Biology, Vanderbilt University, Nashville, Tennessee 37232.
authors.forename: Gautam
authors.initials: G
authors.lastname: Bhave
mesh_terms: D001485:Basement Membrane / Q000378:metabolism*; D024141:Collagen Type IV / Q000235:genetics / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D009195:Peroxidase / Q000235:genetics / Q000378:metabolism*; D043484:Proprotein Convertases / Q000235:genetics / Q000378:metabolism*; D000072417:Protein Domains; D000097423:Peroxidasin
chemical_list: D024141:Collagen Type IV; D016326:Extracellular Matrix Proteins; D009195:Peroxidase; D043484:Proprotein Convertases; D000097423:Peroxidasin
keywords: basement membrane; collagen; collagen IV; extracellular matrix; furin; peroxidase; peroxidasin; proprotein convertase; sulfilimine bond