Matrix metalloproteinases and collagen catabolism.
The matrix metalloproteinase (MMP)/matrixin family has been implicated in both normal tissue remodeling and a variety of diseases associated with abnormal turnover of extracellular matrix components. The mechanism by which MMPs catabolize collagen (collagenolysis) is still largely unknown. Substrate flexibility, MMP active sites, and MMP exosites all contribute to collagen degradation. It has recently been demonstrated that the ability to cleave a triple helix (triple-helical peptidase activity) can be distinguished from the ability to cleave collagen (collagenolytic activity). This suggests that the ability to cleave a triple helix is not the limiting factor for collagenolytic activity-the ability to properly orient and potentially destabilize collagen is. For the MMP family, the catalytic domain can unwind and cleave a triple-helical structure, while the C-terminal hemopexin-like domain appears to be responsible for properly orienting collagen and destabilizing it to some degree. It is also possible that exosites within the catalytic and/or C-terminal hemopexin-like domain may exclude some MMPs from cleaving collagen. Overall, it appears that many proteases of distinct mechanisms possess triple-helical peptidase activity, and that convergent evolution led to a few proteases possessing collagenolytic activity. Proper orientation and distortion of the triple helix may be the key factor for collagenolysis.
Lauer-Fields
Janelle L
JL
Department of Chemistry and Biochemistry, Florida Atlantic University, 777 Glades Road, Boca Raton, FL 33431, USA.
Juska
Darius
D
Fields
Gregg B
GB
D002240:Carbohydrate Sequence; D003094:Collagen / Q000378:metabolism*; D017364:Collagenases / Q000378:metabolism; D010450:Endopeptidases / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010455:Peptides / Q000378:metabolism; D011485:Protein Binding / Q000502:physiology; D017434:Protein Structure, Tertiary
D010455:Peptides; D003094:Collagen; D010450:Endopeptidases; D017364:Collagenases; D020782:Matrix Metalloproteinases