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.