Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
National Philanthropic Trust

Site Tools

  • AAAS
  • Subscribe
  • Feedback

Site Search

Search Advanced

Science 1 October 2004:
Vol. 306. no. 5693, pp. 108 - 111
DOI: 10.1126/science.1099179
Prev | Table of Contents | Next

Reports

Interstitial Collagenase Is a Brownian Ratchet Driven by Proteolysis of Collagen

Saveez Saffarian,1 Ivan E. Collier,2 Barry L. Marmer,2 Elliot L. Elson,1 Gregory Goldberg1,2*

We show that activated collagenase (MMP-1) moves processively on the collagen fibril. The mechanism of movement is a biased diffusion with the bias component dependent on the proteolysis of its substrate, not adenosine triphosphate (ATP) hydrolysis. Inactivation of the enzyme by a single amino acid residue substitution in the active center eliminates the bias without noticeable effect on rate of diffusion. Monte Carlo simulations using a model similar to a "burnt bridge" Brownian ratchet accurately describe our experimental results and previous observations on kinetics of collagen digestion. The biological implications of MMP-1 acting as a molecular ratchet tethered to the cell surface suggest new mechanisms for its role in tissue remodeling and cell-matrix interaction.

1 Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, MO 63110, USA.
2 Division of Dermatology, Washington University School of Medicine, St. Louis, MO 63110, USA.

* To whom correspondence should be addressed. E-mail: goldberg{at}medicine.wustl.edu

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
MMP-12 Catalytic Domain Recognizes Triple Helical Peptide Models of Collagen V with Exosites and High Activity.
R. Bhaskaran, M. O. Palmier, J. L. Lauer-Fields, G. B. Fields, and S. R. Van Doren (2008)
J. Biol. Chem. 283, 21779-21788
   Abstract »    Full Text »    PDF »
Collagen fibril architecture, domain organization, and triple-helical conformation govern its proteolysis.
S. Perumal, O. Antipova, and J. P. R. O. Orgel (2008)
PNAS 105, 2824-2829
   Abstract »    Full Text »    PDF »
The Roles of Substrate Thermal Stability and P2 and P1' Subsite Identity on Matrix Metalloproteinase Triple-helical Peptidase Activity and Collagen Specificity.
D. Minond, J. L. Lauer-Fields, M. Cudic, C. M. Overall, D. Pei, K. Brew, R. Visse, H. Nagase, and G. B. Fields (2006)
J. Biol. Chem. 281, 38302-38313
   Abstract »    Full Text »    PDF »
Activation of EDTA-Resistant Gelatinases in Malignant Human Tumors..
D. Chen, A. Kennedy, J.-Y. Wang, W. Zeng, Q. Zhao, M. Pearl, M. Zhang, Z. Suo, J. M. Nesland, Y. Qiao, et al. (2006)
Cancer Res. 66, 9977-9985
   Abstract »    Full Text »    PDF »
A cancer cell metalloprotease triad regulates the basement membrane transmigration program.
K. Hotary, X.-Y. Li, E. Allen, S. L. Stevens, and S. J. Weiss (2006)
Genes & Dev. 20, 2673-2686
   Abstract »    Full Text »    PDF »


ADVERTISEMENT
Click Me!

ADVERTISEMENT
Click Me!

To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)