Specific collagenolysis by gelatinase A, MMP-2, is determined by the hemopexin domain and not the fibronectin-like domain.
In view of the essential role of the hemopexin domain of the traditional interstitial collagenases, MMP-1, -8, -13 and MT1-MMP (MMP-14), in determining specific collagen cleavage we have studied the function of this domain in MMP-2, relative to that of the fibronectin-like domain that promotes gelatinolysis. Although the fibronectin-like domain promotes avid binding to collagen, our data demonstrate that the catalytic and hemopexin domains of MMP-2 are sufficient to effect the critical step in cleavage of rat type I collagen into 3/4 and 1/4 fragments. The mechanism of MMP-2 cleavage of collagen proceeds in two phases, the first resembling that of the interstitial collagenases, followed by gelatinolysis, promoted by the fibronectin-like domain.
Patterson
M L
ML
School of Biological Sciences, University of East Anglia, Norwich, NR4 7TJ, UK.
Atkinson
S J
SJ
Knäuper
V
V
Murphy
G
G
D000818:Animals; D001665:Binding Sites; D002417:Cattle; D003094:Collagen / Q000378:metabolism*; D005353:Fibronectins / Q000737:chemistry; D006466:Hemopexin / Q000737:chemistry; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D020778:Matrix Metalloproteinase 2 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D017434:Protein Structure, Tertiary; D051381:Rats; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
D005353:Fibronectins; D011994:Recombinant Proteins; D003094:Collagen; D006466:Hemopexin; D020778:Matrix Metalloproteinase 2