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According to a report on the MIT Web site, collagen makes up about 30% of the human body. It is an important component of muscle, skin, bones and cartilage, and forms scar tissue. However, a lesser-known function of collagen is what piqued the interest of Stultz: its ability to become flexible and break down.
Collagen has traditionally been thought of as a rigid molecule. For decades, scientists have reportedly been trying to understand the relationship between collagen and the collagenase enzymes that break it down. Structural studies requiring crystallization of the protein have reportedly shown collagen to be a tightly wound triple helix, which puzzled scientists because this architectures offers no access for collagenase enzymes to bind to it and break it down. One would not expect collagen to broken up by these enzymes.
Thus, Stultz suspected that the low temperatures required to crystallize collagen could be masking some aspect of the protein structure. Computer modeling suggested that higher temperatures, such as room or body temperature, would allow some sections of the collagen molecule to unwind, becoming floppy and in turn opening up sites to fit collagenase, thus breaking down the protein.
According to the report, Stultz and paper co-authors Ramon Salsas-Escat, a graduate student, and Paul Nerenberg, PhD, tested the theory by exposing room-temperature collagen to a mutated form of collagenase that only recognizes unfolded collagen. Previous work had shown no degradation under such conditions but the researchers waited longer, up to six days, and found that some of the collagen was broken down. They also found the percentage of floppy collagen molecules at any given time depended upon the temperature.
Over the past couple of decades, researchers have reportedly tried to develop drugs to inhibit collagenase enzymes, to prevent arterial plaques from rupturing. Stultz’s new findings, however, raise the possibility of targeting the collagen itself, rather than the enzyme. That is, they could potentially make collagen more rigid so it will not be susceptible to collagenase degradation.