title: The Ancient Immunoglobulin Domains of Peroxidasin Are Required to Form Sulfilimine Cross-links in Collagen IV.
abstract: The collagen IV sulfilimine cross-link and its catalyzing enzyme, peroxidasin, represent a dyad critical for tissue development, which is conserved throughout the animal kingdom. Peroxidasin forms novel sulfilimine bonds between opposing methionine and hydroxylysine residues to structurally reinforce the collagen IV scaffold, a function critical for basement membrane and tissue integrity. However, the molecular mechanism underlying cross-link formation remains unclear. In this work, we demonstrate that the catalytic domain of peroxidasin and its immunoglobulin (Ig) domains are required for efficient sulfilimine bond formation. Thus, these molecular features underlie the evolutionarily conserved function of peroxidasin in tissue development and integrity and distinguish peroxidasin from other peroxidases, such as myeloperoxidase (MPO) and eosinophil peroxidase (EPO).
authors.affiliation: From the Division of Nephrology and Hypertension and Department of Medicine, Center for Matrix Biology.
authors.forename: Isi A
authors.initials: IA
authors.lastname: Ero-Tolliver
authors.affiliation: From the Division of Nephrology and Hypertension and Department of Medicine, Center for Matrix Biology, Departments of Biochemistry and Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee 37232.
authors.forename: Billy G
authors.initials: BG
authors.lastname: Hudson
authors.affiliation: From the Division of Nephrology and Hypertension and Department of Medicine, Center for Matrix Biology, gautam.bhave@vanderbilt.edu.
authors.forename: Gautam
authors.initials: G
authors.lastname: Bhave
mesh_terms: D024141:Collagen Type IV / Q000378:metabolism*; D003432:Cross-Linking Reagents / Q000378:metabolism*; D019143:Evolution, Molecular; D005109:Extracellular Matrix / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000737:chemistry* / Q000378:metabolism*; D057809:HEK293 Cells; D006418:Heme / Q000378:metabolism; D006801:Humans; D007097:Imines / Q000378:metabolism*; D007136:Immunoglobulins / Q000737:chemistry*; D008954:Models, Biological; D009195:Peroxidase / Q000737:chemistry* / Q000378:metabolism*; D010544:Peroxidases / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D000097423:Peroxidasin
chemical_list: D024141:Collagen Type IV; D003432:Cross-Linking Reagents; D016326:Extracellular Matrix Proteins; D006418:Heme; D007097:Imines; D007136:Immunoglobulins; D009195:Peroxidase; D010544:Peroxidases; D000097423:Peroxidasin; C586946:sulfilimine
keywords: basement membrane; collagen IV; extracellular matrix; myeloperoxidase; peroxidase; peroxidasin; protein cross-linking; sulfilimine bond