Collagen cross-linking: insights on the evolution of metazoan extracellular matrix

Abstract

Collagens constitute a large family of extracellular matrix (ECM) proteins that play a fundamental role in supporting the structure of various tissues in multicellular animals. The mechanical strength of fibrillar collagens is highly dependent on the formation of covalent cross-links between individual fibrils, a process initiated by the enzymatic action of members of the lysyl oxidase (LOX) family. Fibrillar collagens are present in a wide variety of animals, therefore often being associated with metazoan evolution, where the emergence of an ancestral collagen chain has been proposed to lead to the formation of different clades. While LOX-generated collagen cross-linking metabolites have been detected in different metazoan families, there is limited information about when and how collagen acquired this particular modification. By analyzing telopeptide and helical sequences, we identified highly conserved, potential cross-linking sites throughout the metazoan tree of life. Based on this analysis, we propose that they have importantly contributed to the formation and further expansion of fibrillar collagens.

Production of recombinant human procollagen type I C-terminal propeptide and establishment of a sandwich ELISA for quantification

“…Despite the co-expression of several procollagen types in the same cells, each type of procollagen precisely assembles with the cognate polypeptide α chain 1 . This strict chain selectivity during the intracellular trimerization of different collagen types is conferred by the C-propeptide domains, particularly by a highly variable discontinuous sequence of 15 amino acids within the domains, called the chain recognition motif 14 , 28 . PICPα1 and PICPα2 have the 15-residue chain recognition motif of 1339 GGQGSDPADVAI 1350 .. 1359 STE 1361 and 1241 NVEGVTSKEMAT 1252 .. 1261 ANY 1263 , respectively 29 .…”

Roles of the endoplasmic reticulum–resident, collagen-specific molecular chaperone Hsp47 in vertebrate cells and human disease

“…However, in mammals, the Bip gene does not include a heat shock element. Hsp47 is conserved at least in vertebrates, although collagen is conserved in all multicellular animals (37,38). Analysis of the gene structure and genomic organization of Hsp47/SerpinH1 in vertebrate genomes revealed an ancestral Hsp47/SerpinH1 locus in Japanese lamprey (Lethenteron japonicum), which has remained on the same or similar locus for ϳ500 million years (37).…”

Induction of LOX by TGF‐β1/Smad/AP‐1 signaling aggravates rat myocardial fibrosis and heart failure

“…Myocardial fibrosis is the end stage of the development of various cardiovascular diseases. Lysyl oxidase (LOX) is a copper‐dependent amine oxidase that implicates in catalyzing the cross‐linking of collagen and elastin residues in the extracellular matrix (ECM), promoting the collagen deposition, thereby maintaining the structure and normal function of ECM . Increased expression of LOX is associated with fibrosis and cardiac dysfunction .…”