Interstitial collagenase is a Brownian ratchet driven by proteolysis of collagen.
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.
Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, MO 63110, USA.
Saveez
S
Saffarian
Ivan E
IE
Collier
Barry L
BL
Marmer
Elliot L
EL
Elson
Gregory
G
Goldberg
D000255:Adenosine Triphosphate / Q000378:metabolism; D019943:Amino Acid Substitution; D000818:Animals; D003094:Collagen / Q000378:metabolism*; D003198:Computer Simulation; D004058:Diffusion; D005453:Fluorescence; D006801:Humans; D006868:Hydrolysis; D008433:Mathematics; D020781:Matrix Metalloproteinase 1 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D008956:Models, Chemical; D020409:Molecular Motor Proteins / Q000737:chemistry / Q000378:metabolism; D009010:Monte Carlo Method; D017354:Point Mutation; D021381:Protein Transport; D051381:Rats; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism
D020409:Molecular Motor Proteins; D011994:Recombinant Proteins; D000255:Adenosine Triphosphate; D003094:Collagen; D020781:Matrix Metalloproteinase 1