U.S. Department of Health and Human Services

A New Chemical Bond in Collagen IV Networks

Researchers have discovered a new kind of chemical bond in biological tissue, a fundamental discovery in structural biology that may provide insights into several human diseases. The bond connects two of the subunits that make up collagen IV, a protein that is an important component of the extracellular matrix. Collagen provides structural support to tissues, serves as a scaffold upon which other complexes are assembled, and mediates cellular signaling. Scientists have long known that collagen subunits are linked to one another through intermolecular bonds that lend strength and structural integrity to the matrix; however, the precise nature of these bonds had eluded them. Using advanced techniques to study protein structure, the researchers discovered a novel chemical bond between a sulfur atom of the amino acid methionine on one subunit and a nitrogen atom of a modified form of the amino acid lysine on another. This is the first time that a “sulfilimine” bond – a direct bond between sulfur and nitrogen atoms – has been found in a native biomolecule. 

Collage IV networks have been implicated in a number of human diseases. Two collagen subunits are defective in the inherited kidney disorder, Alport syndrome, a condition in which waste filtering by the kidney is impaired due to disruption of the extracellular matrix. Furthermore, one collagen chain is involved in the rare, autoimmune kidney disease, Goodpasture syndrome. In this disease, the misguided antibody attack on the kidney’s extracellular matrix is thought to be due to exposure of a usually-hidden part of the collagen molecule, which may be made accessible as a consequence of the absence or breakage of the sulfilimine bond. Discovery of this novel chemical bond therefore represents not only an important advance in our knowledge of collagen structure, but also may identify causes of disease and possible treatment approaches.​

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Vanacore R, Ham AJ, Voehler M, Sanders CR, Conrads TP, Veenstra TD, Sharpless KB, Dawson PE, Hudson BG: A sulfilimine bond identified in collagen IV. Science 325: 1230-1234, 2009.