Structure and Behavior of Collagen Revealed Utilizing Photon Technology

The structure and behavior of one of the most common proteins have been resolved at a level of clarity never before seen, due to recently developed technology.

The new research was performed by investigators from the Advanced Photon Source (APS) at the U.S. Department of Energy's (DOE) Argonne U.S. National Laboratory (Argonne, IL, USA). Illinois Institute of Technology (Chicago, IL, USA) biologist Dr. Joseph Orgel used the high-energy X-rays produced by the APS to examine the structure of collagen, a protein that composes more than one-quarter of all proteins in the human body and forms the principal component of skin, teeth, ligaments, the heart, blood vessels, bones, and cartilage. In these tissues, collagen molecules bunch themselves into overlapping bundles called fibrils. These fibrils, each containing billions of atoms, entangle themselves into collagen fibers that are visible to the naked eye.

Scientists have known the basic molecular structure of collagen since the 1950s, when several different international groups of scientists discovered that it had a triple-stranded helical structure. However, researches had never before had the ability to evaluate the structure of an entire fibril in the same way that they could study an individual collagen molecule, according to Dr. Orgel.

Dr. Orgel and his team performed diffraction studies on intact collagen fibrils inside the tendons of rat-tails to determine just how the protein functioned within unbroken tissue. "We tried to draw a highly accurate map of the molecular structure of tissues,” Dr. Orgel said. "By doing so, we hope to transform a very basic understanding that we have of the molecular structure of tissue into a much more tangible form.”

Since the scientists kept the tendon tissue intact, they could see how the collagen molecule binds to collagenases, a class of enzymes which when working correctly, help to regulate the normal growth and development of animals but when malfunctioning can lead to the metastasis of cancerous tumors or rheumatoid arthritis. The visualization of this interaction could help drug developers to create an inhibitor to prevent the pathologic action of the enzyme, according to Dr. Orgel.

Earlier research of the structure of collagen had looked only at crystals of small fragments of the protein, so scientists had little knowledge of how it looked within intact tissue. "It's impossible to get the information that we did by removing tiny chunks of the tissue,” Dr. Orgel said. "We couldn't obtain these data by single-crystal crystallography. This research was made possible only because of the BioCAT beamline provided by the APS.”

The research was published in the February 26, 2008, issue of the Proceedings of the [U.S.] National Academy of Sciences (PNAS).


Related Links:
Argonne National Laboratory