Interstitial collagenase is a brownian ratchet driven by proteolysis of collagen

Saveez Saffarian, Ivan E. Collier, Barry L. Marmer, Elliot L. Elson, Gregory Goldberg

Research output: Contribution to journalArticle

134 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)108-111
Number of pages4
JournalScience
Volume306
Issue number5693
DOIs
StatePublished - Oct 1 2004

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