title: Human inter-α-inhibitor is a substrate for factor XIIIa and tissue transglutaminase.
abstract: In this study, we show that inter-α-inhibitor is a substrate for both factor XIIIa and tissue transglutaminase. These enzymes catalyze the incorporation of dansylcadaverine and biotin-pentylamine, revealing that inter-α-inhibitor contains reactive Gln residues within all three subunits. These findings suggest that transglutaminases catalyze the covalent conjugation of inter-α-inhibitor to other proteins. This was demonstrated by the cross-linking between inter-α-inhibitor and fibrinogen by either factor XIIIa or tissue transglutaminase. Finally, using quantitative mass spectrometry, we show that inter-α-inhibitor is cross-linked to the fibrin clot in a 1:20 ratio relative to the known factor XIIIa substrate α2-antiplasmin. This interaction may protect fibrin or other Lys-donating proteins from adventitious proteolysis by increasing the local concentration of bikunin. In addition, the reaction may influence the TSG-6/heavy Chain 2-mediated transfer of heavy chains observed during inflammation.
authors.affiliation: Department of Molecular Biology, University of Aarhus, Aarhus, Denmark. csss@mb.au.dk
authors.forename: Carsten
authors.initials: C
authors.lastname: Scavenius
authors.forename: Kristian W
authors.initials: KW
authors.lastname: Sanggaard
authors.forename: Camilla L
authors.initials: CL
authors.lastname: Nikolajsen
authors.forename: Steffen
authors.initials: S
authors.lastname: Bak
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Valnickova
authors.forename: Ida B
authors.initials: IB
authors.lastname: Thøgersen
authors.forename: Ole N
authors.initials: ON
authors.lastname: Jensen
authors.forename: Peter
authors.initials: P
authors.lastname: Højrup
authors.forename: Jan J
authors.initials: JJ
authors.lastname: Enghild
mesh_terms: D000510:Alpha-Globulins / Q000737:chemistry / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D020134:Catalytic Domain; D003432:Cross-Linking Reagents / Q000494:pharmacology; D026122:Factor XIIIa / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology; D005340:Fibrinogen / Q000737:chemistry / Q000378:metabolism; D006168:Guinea Pigs; D006801:Humans; D008954:Models, Biological; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D025941:Protein Interaction Mapping; D021122:Protein Subunits / Q000378:metabolism; D013379:Substrate Specificity; D011503:Transglutaminases / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology
chemical_list: D000510:Alpha-Globulins; D003432:Cross-Linking Reagents; D021122:Protein Subunits; C011877:inter-alpha-inhibitor; D005340:Fibrinogen; D026122:Factor XIIIa; C532876:TGM6 protein, human; D011503:Transglutaminases