Article (Scientific journals)
Differential cleavage of lysyl oxidase by the metalloproteinases BMP1 and ADAMTS2/14 regulates collagen binding through a tyrosine sulfate domain.
Rosell-García, Tamara; Paradela, Alberto; Bravo, Gema et al.
2019In Journal of Biological Chemistry, 294 (29), p. 11087-11100
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Abstract :
[en] Collagens are the main structural component of the extracellular matrix and provide biomechanical properties to connective tissues. A critical step in collagen fibril formation is the proteolytic removal of N- and C-terminal propeptides from procollagens by metalloproteinases of the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) and BMP1 (bone morphogenetic protein 1)/Tolloid-like families, respectively. BMP1 also cleaves and activates the lysyl oxidase (LOX) precursor, the enzyme catalyzing the initial step in the formation of covalent collagen cross-links, an essential process for fibril stabilization. In this study, using murine skin fibroblasts and HEK293 cells, along with immunoprecipitation, LOX enzymatic activity, solid-phase binding assays, and proteomics analyses, we report that the LOX precursor is proteolytically processed by the procollagen N-proteinases ADAMTS2 and ADAMTS14 between Asp-218 and Tyr-219, 50 amino acids downstream of the BMP1 cleavage site. We noted that the LOX sequence between the BMP1- and ADAMTS-processing sites contains several conserved tyrosine residues, of which some are post-translationally modified by tyrosine O-sulfation and contribute to binding to collagen. Taken together, these findings unravel an additional level of regulation in the formation of collagen fibrils. They point to a mechanism that controls the binding of LOX to collagen and is based on differential BMP1- and ADAMTS2/14-mediated cleavage of a tyrosine-sulfated domain.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Rosell-García, Tamara
Paradela, Alberto
Bravo, Gema
Dupont, Laura ;  Université de Liège - ULiège > GIGA Cancer - Connective Tissue Biology
Bekhouche, Mourad
Colige, Alain  ;  Université de Liège - ULiège > Cancer-Connective Tissue Biology
Rodriguez-Pascual, Fernando 
 These authors have contributed equally to this work.
Language :
Title :
Differential cleavage of lysyl oxidase by the metalloproteinases BMP1 and ADAMTS2/14 regulates collagen binding through a tyrosine sulfate domain.
Publication date :
19 July 2019
Journal title :
Journal of Biological Chemistry
Publisher :
American Society for Biochemistry and Molecular Biology, United States - Maryland
Volume :
Issue :
Pages :
Peer reviewed :
Peer Reviewed verified by ORBi
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since 31 January 2020


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