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Molecular motor implicated in tissue remodeling

St. Louis, Sept. 30, 2004--A well-known enzyme present in the skin and other tissues turns out to be a molecule-sized motor that extracts its fuel from the road it runs on, according to researchers at Washington University School of Medicine in St. Louis. Their discovery appears in the Oct. 1 issue of Science.

The enzyme, MMP-1, is a member of a group of enzymes that breaks down collagen, a fibrous substance that constitutes the foundation of the extracellular matrix that supports the cells in the body's tissues.

"By digesting collagen, enzymes such as MMP-1 initiate tissue remodeling, which can have a variety of purposes from organ development to tissue repair to metastatic invasion of tumors," says senior author Gregory Goldberg, Ph.D., professor of dermatology and of biochemistry and molecular biophysics. "Because they participate in all basic tissue metabolism, we want to understand how they function."

Goldberg and his colleagues Savees Saffarian, Ivan Collier, Barry Marmer and Elliot Elson found that MMP-1 operates as a molecular motor--a molecule that converts chemical energy into motion. "This is the only extracellular motor known," says Elson, Ph.D., coauthor and professor of biochemistry and molecular biophysics.

The research team discovered that MMP-1 moves along a collagen filament with a net unidirectional motion. One-way motion indicates that energy is being utilized, so the team looked for an energy source.

While most molecules that act as motors are inside cells and get their energy from a ubiquitous high-energy molecule called ATP, the team found that MMP-1 gets its energy by breaking the molecular bonds in the collagen filament it is attached to.

"In fact," Goldberg says, "with our model, a whole new principle emerges in which molecular motors in the extracellular matrix operate by extracting energy from the very track they move upon."

The researchers propose that the molecular motor contrib
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Contact: Gwen Ericson
ericsong@wustl.edu
314-286-0141
Washington University School of Medicine
30-Sep-2004


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