New Enzyme Structure Discovery Could Lead To Drugs That Slow Aging Process

Scientists now know what an enzyme important in aging and cancer really looks like. A new study, published Wednesday in Nature, describes the structure of telomerase in more detail than has ever been done before.

Telomerase helps maintain chunks of DNA at the ends of our chromosomes called telomeres. Telomeres are like the caps at the tip of a high heel—over time, they get ground down until there's nothing left. As a result, telomeres are often used as a shorthand for cellular aging—the shorter the telomeres, the older the cell (and the person to whom it belongs).

Researchers already had a good idea how a bunch of pieces of telomerase are built—but no one had put the pieces together. "The previous images were just blotches, really," researcher and study author Kathleen Collins told Newsweek.

What Collins and her colleagues at the University of California, Berkeley, the Lawrence Berkeley National Laboratory and the Howard Hughes Medical Institute did is like a 3D version of a child's puzzle board. They had the pieces; they just didn't know exactly what shape all the pieces needed to fit within.

Telomerase also repairs chromosomal caps to make sure the cell's DNA is in decent shape when it divides. It's also affected by some genetic disorders and may be an interesting way to target cancer; tumor cells don't seem to have their telomeres wear down, even though cells are dividing a lot.

Because telomerase seems linked with aging, people have been hoping it might be possible to mess with it—and finding a drug might be easier if people knew what it looks like. A protein's structure and shape can give clues to spaces where a drug might bind or how it might interact, for example.

Elizabeth Blackburn and her colleagues won a Nobel Prize in 2009 for discovering telomerase but figuring out its structure was difficult.

To determine what a protein looks like, you need to be able to take a picture at a microscopic level. Not only is lots of telomerase hard to find, but it's also very flexible.

In order to get a picture of it, then, the telomerase had to be frozen and then put into a vacuum for an electron microscope. Even after its frozen, telomerase and other biological molecules are very fragile. So Eva Nogales, another of the study's authors, and her colleagues had to take a lot of images using very little power and then stitch them together.

"It had to be Cryo-EM. It really couldn't be anything else," Nogales said.

However, there's still more work to be done before drug companies can really use telomerase's structure to design drugs. The picture that Collins, Nogales and their team have been able to build isn't quite at a high enough resolution—but they're already working on a way to get an even more refined look at the protein.

Even a structure at this resolution is already making a splash. "I'm sure it will have a long-lasting impact," Collins said. "We've been waiting for this structure for a very long time."