Abstract
Interactions of the extracellular matrix (ECM) with domains of matrix metalloproteinases (MMPs) increase their proteolytic action upon matrix components. This occurs by multiple structural means. The activating interactions of a partner protein with pro-MMP-9 and of GAGs with pro-MMP-7 were reported. The interactions of fibrillar proteins with catalytic domains can traverse the breadth of the active site cleft and overflow into a neighboring exosite and perhaps beyond. Exosite interactions bear some resemblance to precedents in thrombin complexes. Basket-shaped surfaces on fibronectin II-like modules (inserted into the catalytic domains of MMP-2 and -9) appear to bind protein fibrils, may bend them, and certainly unwind triple helices. C-terminal hemopexin domains are joined loosely to the catalytic domain, which might facilitate positioning and movement across collagen triple helices. At least the first blade of the β-propeller of the hemopexin domain of MMP-1 seems to interact with the triple helix. Unifying themes among diverse interactions of MMPs with ECM polymers are (1) that two domains of the MMP often participate and (2) that the interaction guides the MMP to the site for proteolytic action.
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- CBD:
-
Collagen-binding domain composed of three FnII-like modules
- CS:
-
Chondroitin sulfate
- ECM:
-
Extracellular matrix
- FnI:
-
Fibronectin type I
- FnII:
-
Fibronectin type II
- GAGs:
-
Glycosaminoglycans
- HDX:
-
Hydrogen/deuterium exchange
- HDXMS:
-
Hydrogen/deuterium exchange detected by mass spectrometry
- HPX:
-
Hemopexin
- HS:
-
Heparan sulfate
- NMR:
-
Nuclear magnetic resonance
- PAR:
-
Protease-activated receptor
- SAXS:
-
Small angle X-ray scattering
- THP:
-
Triple helical peptide
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Acknowledgments
The author is grateful for the grant support of the NIH (GM57289 to SVD and CA98799 to GB Fields) and American Heart Association (0855714G to SVD) sponsoring his research into MMP interactions with matrix molecules.
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Van Doren, S.R. (2011). Structural Basis of Extracellular Matrix Interactions with Matrix Metalloproteinases. In: Parks, W., Mecham, R. (eds) Extracellular Matrix Degradation. Biology of Extracellular Matrix, vol 2. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-16861-1_6
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