Degradation of the COL1 domain of type XIV collagen by 92-kDa gelatinase.
Type XIV collagen is a newly described member of the fibril-associated collagens with interrupted triple helices (FACITs). Expression of this collagen has been localized to various embryonic tissues, suggesting that it has a functional role in development. All FACITs thus far described (types IX, XII, XIV, and XVI) contain a highly homologous carboxyl-terminal triple helical domain designated COL1. We have studied the capacity of various matrix metalloproteinases (interstitial collagenase, stromelysin, matrilysin, and 92-kDa gelatinase) to degrade the COL1 domain of collagen XIV. We found that only 92-kDa gelatinase cleaves COL1. Furthermore, digestion of whole native collagen XIV by the 92-kDa gelatinase indicates that this enzyme specifically attacks the carboxyl-terminal triple helix-containing region of the molecule. COL1 is cleaved by 92-kDa gelatinase at 30 degrees C, a full 5-6 degrees C below the melting temperature (Tm) of this domain; native collagen XIV is also degraded at 30 degrees C. In comparison to interstitial collagenase degradation of its physiologic native type I collagen substrate, the 92-kDa enzyme cleaved COL1 (XIV) with comparable catalytic efficacy. Interestingly, following thermal denaturation of the COL1 fragment, its susceptibility to 92-kDa gelatinase increases, but only to a degree that leaves it several orders of magnitude less sensitive to degradation than denatured collagens I and III. These data indicate that native COL1 and collagen XIV are readily and specifically cleaved by 92-kDa gelatinase. They also suggest a role for 92-kDa gelatinase activity in the structural tissue remodeling of the developing embryo.
Sires
U I
UI
Department of Medicine, Washington University School of Medicine, Jewish Hospital, St. Louis, Missouri 63110.
Dublet
B
B
Aubert-Foucher
E
E
van der Rest
M
M
Welgus
H G
HG
D000818:Animals; D002384:Catalysis; D002417:Cattle; D003094:Collagen / Q000737:chemistry / Q000378:metabolism*; D017364:Collagenases / Q000378:metabolism; D018093:Gelatinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006023:Glycoproteins / Q000494:pharmacology; D006801:Humans; D006868:Hydrolysis; D019278:Matrix Metalloproteinase 3; D020783:Matrix Metalloproteinase 7; D008666:Metalloendopeptidases / Q000378:metabolism; D051381:Rats; D019714:Tissue Inhibitor of Metalloproteinases
D006023:Glycoproteins; D019714:Tissue Inhibitor of Metalloproteinases; D003094:Collagen; D017364:Collagenases; D018093:Gelatinases; D008666:Metalloendopeptidases; D019278:Matrix Metalloproteinase 3; D020783:Matrix Metalloproteinase 7