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Telomerase structure diagram under cryo electron microscopy

Because of its important role in anti-aging, telomerase has been widely concerned in the past 30 years. People yearn for the way to get a long life, but they have failed many times. In a paper published today in the journal Nature, scientists at University of California at Berkeley have obtained the first clear 3D structure of telomerase, and the discovery of telomerase structure has brought new hope for anti – aging drug research.

People’s understanding of telomere function originated in the 70s of last century. In 1973, the former Soviet Union scientist Alexei Olovnikov put forward the telomere hypothesis. Each time a cell divides, the telomere ends at both ends of the chromosome. He speculated that when the chromosomes were shortened to a certain limit, the cells would lose their ability to divide. This is the first time that humans have linked telomeres to aging, and have triggered a wave of research related to telomere.
By 1984, Carol Greider and Elizabeth Blackburn of the University of California at Berkeley found for the first time in single celled four membrane worms that an enzyme can synthesize DNA at the end of the chromosome and compensate for the loss of telomere by cell division. This enzyme is also called telomerase.
In vivo, telomerase activity is strictly regulated. Subsequent studies have found that in human and other multicellular organisms, telomerase is mainly expressed in the embryonic stage and in cells that need to proliferate, and the activity of telomerase is lost in the mature adult cells. Therefore, many scientists believe that the lack of telomerase is the main cause of aging.
The revolutionary discovery of Greider and Blackburn not only gave two scientists the Nobel prize in 25 years, but also the scientific community and the people to see the dawn of prolonging life: if we could keep telomerase active, the cell could be replicated infinitely.
However, to this day, the study of telomerase has not been able to bring us antiaging drugs, one of the important reasons is that our understanding of this enzyme is still very limited. Today, a paper published in nature brings new hope. The research team, also from the University of California at Berkeley, uses cryo electron microscopy to reveal the 3D molecular structure of telomerase in the human body for the first time, and the breakdown of telomerase structure will provide the potential for the development of targeted drugs.

High resolution image under cryo electron microscopy

Kathleen Collins, a professor of molecular and cellular biology at the University of California at Berkeley, has been groping for 26 years in this field, and she is excited to say, “this research has lasted for a long time and is finally achieved with unremitting efforts.” Collins and her colleague Eva Nogales jointly led the study.

Kathleen Collins (left) and Eva Nogales (right)

Over the past more than 30 years, we have a limited understanding of telomerase structure, only knowing that it is made up of a RNA skeleton and 6 different proteins, but how many proteins that modify the RNA skeleton, whether telomerase is a separate task or a pair, before we do not know. This makes it difficult for scientists to “prescribe the right medicine” and find a way to activate telomerase.
One of the difficulties in telomerase research is to obtain purified telomerase molecules. The first author, Nguyen, was isolated and purified from the University of California at Berkeley. After that, for the first time, the clear 3D structure of the active telomerase was obtained by the most advanced cryo electron microscopy. As a technology commended by the Nobel prize in chemistry last year, cryo electron microscopy can help scientists get the structure that can not crystallize and can not use X rays.

3D structure of telomerase

In this study, they increased the resolution of human telomerase images by 4 times, from the previous 30 to 7~8 (1 =10-10 m). In high-resolution images, researchers finally discovered the real structure of telomerase. Nguyen looked back at the scene: “when I first observed that telomerase contained 11 protein subunits, I was excited to shout, ‘Wow, this is the way they are assembled!'”
The research team is now working towards the goal of raising resolution to 3~4, which is two times the diameter of the carbon atom, and will provide sufficient theoretical support for the design of related drugs.


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