Collagen-binding domain of human plasma fibronectin contains a latent type-IV collagenase.
Cleavage of the 45-kDa gelatin-binding fragment of human plasma fibronectin with fibronectinase resulted in the activation of two forms of metalloproteinase with different substrate specificities. The 40-kDa FN-type-IV collagenase A degrades heat-denatured type-I collagen, laminin and also native collagen type IV. The 27-kDa FN-type-IV collagenase B degrades native collagen type IV, but it does not cleave laminin and only poorly degrades gelatin. Both enzymes begin with the same N-terminal sequence VYQPQPH- (residues 262-268 of fibronectin) but, contrary to the FN-type-IV collagenase A, the FN-type-IV collagenase B has lost the C-terminal region of type I repeats, where the major gelatin-binding determinants of fibronectin are located. The FN-type-IV collagenases A and B are sequentially similar to the middle domain (domain II) of collagenase type IV, secreted by H-ras-transformed human bronchial epithelial cells. Substrate and inhibition specificity of FN-type-IV collagenase A and B are different from those of FN-gelatinase and FN-laminase, isolated previously from the central and C-terminal fibronectin domains, respectively. The substrate specificity of both enzymes, characterized in this study, is also different from that of already known matrix-degrading metalloproteinases.
Lambert Vidmar
S
S
Laboratoire de Chimie des Protéines, Institut Pasteur, Paris, France.
Lottspeich
F
F
Emod
I
I
Imhoff
J M
JM
Keil-Dlouha
V
V
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D003094:Collagen / Q000378:metabolism*; D004789:Enzyme Activation; D005353:Fibronectins / Q000737:chemistry / Q000378:metabolism*; D006358:Hot Temperature; D006801:Humans; D007797:Laminin / Q000378:metabolism; D003012:Microbial Collagenase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008969:Molecular Sequence Data; D008970:Molecular Weight; D010446:Peptide Fragments / Q000378:metabolism; D011489:Protein Denaturation; D051381:Rats; D012697:Serine Endopeptidases / Q000378:metabolism; D013379:Substrate Specificity
D005353:Fibronectins; D007797:Laminin; D010446:Peptide Fragments; D003094:Collagen; D012697:Serine Endopeptidases; C071222:fibronectinase; D003012:Microbial Collagenase