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Unraveling a protein, researchers uncover mechanics of anti-cancer agent

CHAMPAIGN, Ill. -- From within the rich fabric of connecting tissue between cells, researchers of four institutions, led by the University of Illinois at Urbana-Champaign, have identified the action of anastellin, a natural agent that is showing promise blocking metastasis of cancer cells and enhancing wound healing.

That anastellin is derived from the cell adhesion protein fibronectin found in the extracellular matrix surrounding cells was known. Researchers at the Burnham Institute in California in September had documented the molecular structure of anastellin, but its ability to initiate matrix assembly and block the spread of cancer cells remained a mystery.

Using crystallography, atomic force microscopy and advanced computer modeling, researchers sorted the chemical structure and mechanical strength of the known fibronectin proteins that glue together myriads of cells in mammalian body tissues.

In the Dec. 9 issue of the Proceedings of the National Academy of Sciences,
they show that the fibronectin known as FN-III-1 behaves differently mechanically than other type-three modules. The paper was placed online Dec. 1 at the PNAS Web site.

"Type 3-1 stands out," said Klaus Schulten, holder of the Swanlund Chair in Physics at Illinois and director of the theoretical and computational biophysics group at the Beckman Institute for Advanced Science and Technology.

"When stretched mechanically, it extends in two stages, first to about one-third of its total length, then to full length, or about 10 times its initial size," he said. "The first stretch reaches a rather stable intermediate. Other fibronectin type-three modules reach their extended length more quickly."

All fibronectin type-three modules consist of a sandwich structure containing two sheets, but Schulten and his colleagues found that one sheet of 3-1 is much stronger.

"It is mainly this strong sheet that is anastellin, and it stabilizes the stretch
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Contact: Jim Barlow
jebarlow@uiuc.edu
217-333-5802
University of Illinois at Urbana-Champaign
2-Dec-2003


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