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Biological tissue’s ‘glue’ identified

By Bill Snyder
January 2010

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Researchers at Vanderbilt University Medical Center have discovered a novel chemical bond in biological tissue, a fundamental discovery that helps explain evolutionary adaptation and may shed light on human disease.

The novel sulfilimine bond, between a sulfur and a nitrogen atom, acts like a “fastener” to reinforce a collagen IV network found in connective tissue throughout the body. It is “an apparent adaptation crucial for … evolution,” the researchers reported in Science magazine.

“Every tissue in your body has got this bond,” said Billy Hudson, Ph.D., senior author of the paper and director of the Vanderbilt Center for Matrix Biology. “It is the ‘glue’ … that helps hold together the extracellular matrix.”

The extracellular matrix provides structural support in all tissues and molecular cues for influencing cell behavior.

The finding “is just scratching the tip of the iceberg,” added the paper’s lead author, Roberto Vanacore, Ph.D., research assistant professor of Medicine. The Vanderbilt researchers are now searching for the enzyme that makes the bond, and for diseases that may be caused by a defective bond.

Hudson, the Elliot V. Newman professor of Medicine, Biochemistry and Pathology, has been studying the glomerular basement membrane of the kidney for more than 40 years.

The basement membrane, which supports cells in the extracellular matrix, consists largely of type IV collagen. The collagen, in turn, is constructed from a family of proteins called alpha chains that twist around each other to form triple helical “protomers,” like cables supporting a bridge.

While at the University of Kansas Medical School in Kansas City, Hudson and his colleagues discovered two previously unknown alpha chains, which are defective in an inherited kidney disorder called Alport syndrome.

One of the chains, they found, is also involved in a rare, auto-immune kidney disease called Goodpasture syndrome.

There is some evidence that the misguided antibody attack on the kidney’s basement membrane may be triggered by exposure of a previously hidden part of collagen caused by the absence or breakage of the sulfilimine bond, Vanacore said.

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