Matrix metalloproteinase interactions with collagen and elastin

Most abundant in the extracellular matrix are collagens, joined by elastin that confers elastic recoil to the lung, aorta, and skin. These fibrils are highly resistant to proteolysis but can succumb to a minority of the matrix metalloproteinases (MMPs). Considerable inroads to understanding how such MMPs move to the susceptible sites in collagen and then unwind the triple helix of collagen monomers have been gained. The essential role in unwinding of the hemopexin-like domain of interstitial collagenases or the collagen binding domain of gelatinases is highlighted. Elastolysis is also facilitated by the collagen binding domain in the cases of MMP-2 and MMP-9, and remote exosites of the catalytic domain in the case of MMP-12. • Active MMP-1 and MT1-MMP diffuse across collagen in one direction. • Bridging of collagen between domains of MMP-1 may open the triple helix by bending. • MT1-MMP may differ from MMP-1 in mode of binding of the collagen triple helix. • MMP-12 utilizes exosites remote on its catalytic domain in elastolysis.