Regulation of C1-inhibitor function by binding to type IV collagen and heparin.
Serpins inhibit proteinases by a branched pathway, in which an intermediate serpin-proteinase complex can either form a stable covalent serpin-proteinase complex or produce reactive center cleaved serpin in a substrate reaction. It was tested whether these competing reactions could be regulated for the serpin C1-inhibitor by ligand binding. C1-inhibitor bound to type IV collagen, laminin, and entactin. Type IV collagen (10 microg/ml) caused an increase in the stoichiometry of inhibition for C1s inhibition by C1-inhibitor to 1.48 from 1.09 in the absence of ligand. A dose-dependent increase in the stoichiometry up to 1.27 in the presence of 100 microg/ml heparin was also observed. At low ionic strength the stoichiometry increased to 2.55. These data provide the first report that C1-inhibitor can bind to type IV collagen and also show that C 1-inhibitor can be regulated by ligand binding.
Patston
P A
PA
Department of Oral Medicine and Diagnostic Sciences, University of Illinois-Chicago 60612, USA. patston@uic.edu
Schapira
M
M
D001667:Binding, Competitive; D003094:Collagen / Q000378:metabolism*; D003174:Complement C1 Inactivator Proteins / Q000378:metabolism* / Q000494:pharmacology / Q000502:physiology*; D003173:Complement C1s / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D016326:Extracellular Matrix Proteins / Q000378:metabolism / Q000494:pharmacology; D006493:Heparin / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D011485:Protein Binding
D003174:Complement C1 Inactivator Proteins; D016326:Extracellular Matrix Proteins; D006493:Heparin; D003094:Collagen; D003173:Complement C1s