Insights into collagenolytic enzymes
Collagen metabolism is crucial to the maintenance of the structural integrity of mammalian connective tissue. Collagen triple helices form immensely tensile fibrils that link with each other to create interstitial matrices and basement membranes. The timely breakdown of collagen is an important housekeeping mechanism that helps maintain healthy tissues and organs; however, defects in normal collagenolysis have been linked to debilitating diseases such as arthritis, atherosclerosis and cancer. Therefore, there is now a burgeoning interest in gaining a deeper insight into molecular aspects that facilitate collagen degradation.
In a recent minireview in The Journal of Biological Chemistry, Gregg B. Fields of the Torrey Pines Institute for Molecular Studies in Port St. Lucie, Fla., gives an extensive account of the myriad collagenolytic enzymes, the majority of which are matrix metalloproteinases, or MMPs, implicated in mammalian collagen metabolism.
While outlining the distinct methods employed by MMPs in collagen proteolysis, the author also highlights the unique features of the cleavage sites that make different collagen fibers susceptible to the action of specific MMPs. Furthermore, this minireview delves into the molecular mechanisms that underlie the categorical breakdown of the collagen triple helix and elucidates the current models and hypotheses that have determined how MMPs gain access to cleavage sites, the enzyme conformations that are critical for hydrolysis and the diverse modes of proteolysis based on the structural complexities of collagen fibers. The minireview also describes the role of binding proteins such as integrins and processes such as MMP dimerization in providing additional strain on collagen fibers, thus facilitating the collagenolytic program.
This minireview, titled “Interstitial collagen catabolism,” highlights the significance of current research in this field and the potential exploitation of differences in MMP-mediated catabolism for the development of target-specific inhibitors. “As further information on interstitial collagenolytic processes is obtained, inhibition can be fine-tuned to be disease- or pathogen-specific,” writes the author.
Aditi S. Iyengar (firstname.lastname@example.org) is a graduate student in the genetics department at Louisiana State University Health Sciences Center in New Orleans.