Human 92 kDa type IV collagenase: functional analysis of fibronectin and carboxyl-end domains.
Two closely related secreted metalloproteases 72 and 92 kDa type IV collagenases (72- and 92T4Cl) consist of several structural domains, the functions of which are poorly understood. Both metalloproteases can bind to gelatin as well as form complexes with specific inhibitors in the proenzyme form. The biologic role of the proenzyme-inhibitor complex formation remained unclear. Here we summarize results demonstrating that the fibronectin-like domain of 92T4Cl mediates gelatin binding of the proenzyme, while the hemopexin like carboxy-terminal domain is essential for the complex formation of the proenzyme with TIMP. The formation of a 92T4Cl proenzyme complex with TIMP prevents dimerization, formation of the novel complex with ClI proenzyme, and activation of the 92T4Cl by stromelysin. Conversely, formation of the covalent 92T4Cl homodimer excludes the formation of a proenzyme-TIMP complex, thus allowing this form of enzyme to enter into the proteolytic cascade of activation. Both components of the 92T4Cl-ClI complex can be activated in a fashion similar to that of free enzymes, yielding a complex active against both gelatin and fibrillar collagen.
Strongin
A Y
AY
Division of Dermatology, Washington University School of Medicine, St. Louis, Missouri.
Collier
I E
IE
Krasnov
P A
PA
Genrich
L T
LT
Marmer
B L
BL
Goldberg
G I
GI
D000595:Amino Acid Sequence; D001665:Binding Sites; D017364:Collagenases / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D004789:Enzyme Activation / Q000187:drug effects; D004792:Enzyme Precursors / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D005353:Fibronectins / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D005780:Gelatin; D006023:Glycoproteins; D006801:Humans; D066298:In Vitro Techniques; D019278:Matrix Metalloproteinase 3; D020780:Matrix Metalloproteinase 9; D008666:Metalloendopeptidases / Q000494:pharmacology; D008969:Molecular Sequence Data; D008970:Molecular Weight; D016297:Mutagenesis, Site-Directed; D017386:Sequence Homology, Amino Acid; D019714:Tissue Inhibitor of Metalloproteinases
D004792:Enzyme Precursors; D005353:Fibronectins; D006023:Glycoproteins; D019714:Tissue Inhibitor of Metalloproteinases; D005780:Gelatin; D017364:Collagenases; D008666:Metalloendopeptidases; D019278:Matrix Metalloproteinase 3; D020780:Matrix Metalloproteinase 9