title: Carbamylation differentially alters type I collagen sensitivity to various collagenases.
abstract: Carbamylation is a post-translational modification due to nonenzymatic binding of cyanate, a by-product of urea, on free amino groups of proteins. Post-translational modifications are known to induce alterations in structural and functional properties of proteins, thus disturbing protein-protein or cell-protein interactions. We report the impact of carbamylation on type I collagen sensitivity to enzymatic proteolysis. Type I collagen was extracted from rat tail tendons and carbamylated by incubation with 0.1 M potassium cyanate at 37 degrees C for 2, 6 or 24 h. Degradation assays revealed that carbamylated collagen exhibited a greater resistance to collagenases (i.e. bacterial collagenase, matrix metalloproteinase(MMP)-1, MMP-8 and MMP-13), together with an increased sensitivity to MMP-2. Evaluation of collagen triple helix conformation by polarimetry indicated that local destabilizations of triple helix structure related to carbamylation could be responsible for the observed differences in sensitivity. These results confirm the crucial role of triple helix integrity in the degradation of type I collagen by MMPs, and support the deleterious impact of post-translational modifications in vivo by altering the balanced remodeling of collagen within connective tissue.
authors.affiliation: Laboratory of Biochemistry and Molecular Biology, CNRS UMR 6198, IFR53 Biomolecules, Faculty of Medicine, University of Reims Champagne Ardenne, 51 rue Cognacq Jay, 51095 Reims Cedex, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Jaisson
authors.forename: Véronique
authors.initials: V
authors.lastname: Larreta-Garde
authors.forename: Georges
authors.initials: G
authors.lastname: Bellon
authors.forename: William
authors.initials: W
authors.lastname: Hornebeck
authors.forename: Roselyne
authors.initials: R
authors.lastname: Garnotel
authors.forename: Philippe
authors.initials: P
authors.lastname: Gillery
mesh_terms: D000818:Animals; D002219:Carbamates / Q000378:metabolism*; D024042:Collagen Type I / Q000737:chemistry / Q000378:metabolism*; D017364:Collagenases / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D020836:Protein Structure, Quaternary; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D002219:Carbamates; D024042:Collagen Type I; D017364:Collagenases