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VCU-led discovery of new protein shape could impact cancer and neurodegenerative disease therapies

The protein has a role in the growth and repair of other proteins.

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Qinglian Liu, Ph.D., has found a new shape for the common protein Hsp70. The discovery could impact the development of therapeutics for cancer and neurodegenerative diseases.
Photo by Allen Jones, University Marketing

A Virginia Commonwealth University researcher has discovered a new conformation of a common protein group with links to cancer metastasis and neurodegenerative diseases. 

Qinglian Liu, Ph.D., an associate professor in the Department of Physiology and Biophysics at VCU School of Medicine and research member at Massey Cancer Center, recently found a third variation in the structure of the protein type Hsp70, which is responsible for the growth and repair of other proteins. The findings were published in the journal Nature Communications on Oct. 31. The discovery could eventually lead to the development of small molecules that could either improve or curtail the function of Hsp70.

Hsp70, or 70 kilodalton heat shock protein, accounts for about 2 percent of the more than 100,000 protein types in the human body. The protein is a chaperone, which means it helps other proteins develop a shape. A protein’s shape helps determine its function. When proteins lose their shape from deterioration due to illnesses such as fevers, or from environmental stressors such as overexposure to sunlight, Hsp70 helps them reform.

“Everything we do, we can do because proteins function,” said. “Our cells are made of proteins and they all must fulfill their roles, similar to how everyone has a specific job in our society. She added that the role of Hsp70 is maintaining the health of proteins.

Finding the third shape of Hsp70 helps researchers uncover the biochemical function of this protein group.

“Understanding how the three shapes fit together reveals the process that Hsp70 goes through to fold proteins,” Liu said. “When you see all the shapes together, you can picture a video of them working in sequence to fold a protein.”

The first Hsp70 shape was discovered in 1996. Liu found the second shape in 2012 and more shapes await discovery after Liu’s most recent finding.

Hsp70’s ability to fold proteins and rebuild them once they lose their shape may hold part of the key to cures for cancer and certain neurological diseases, Liu said.

An overabundance of Hsp70 has been linked to cancer metastasis. Hsp70 can cause the proteins in cancer cells to continually fold, which exacerbates cell growth.

The opposite problem occurs in patients with neurodegenerative diseases such as Alzheimer’s and Parkinson’s disease. In the case of Alzheimer’s, patients experience dangerous protein aggregates in the brain called amyloid plaques. Instead of being repaired after losing their shape, the proteins form these harmful buildups because there are not enough Hsp70s available to refold the proteins.

“We cannot survive without Hsp70, but it must be balanced,” Liu said. “We can’t have too much or too little. Once we understand more about Hsp70’s activity, we can design small molecules to modulate the activity of the protein, which could prevent or slow the growth of certain diseases.”

 

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About the VCU Massey Cancer Center

VCU Massey Cancer Center is one of only 68 National Cancer Institute-designated institutions in the country that leads and shapes America’s cancer research efforts. Working with all kinds of cancers, Massey conducts basic, translational and clinical cancer research, provides state-of-the-art treatments and clinical trials, and promotes cancer prevention and education. Since 1974, Massey has served as an internationally recognized center of excellence. It offers the most cancer clinical trials in Virginia and serves patients at 10 locations. Its 1,000-plus researchers, clinicians and staff members are dedicated to improving the quality of human life by developing and delivering effective means to prevent, control and ultimately cure cancer. Visit Massey online at www.massey.vcu.edu or call 877-4-MASSEY for more information.