Discovery of new protein shape could impact cancer and neurodegenerative disease therapies

December 13, 2017 by Leah Small, Virginia Commonwealth University

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, recently found a third variation in the structure of the protein type Hsp70, which is responsible for the growth and repair of other proteins. Her 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 , 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," Liu 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 . Hsp70 can cause the proteins in cancer cells to continually fold, which exacerbates cell growth.

The opposite problem occurs in patients with such as Alzheimer's and Parkinson's . In the case of Alzheimer's, patients experience dangerous protein aggregates in the brain called amyloid plaques. Instead of being repaired after losing their , 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 to modulate the activity of the , which could prevent or slow the growth of certain diseases."

Explore further: Universal clamping protein stabilizes folded proteins: New insight into how the chaperone protein Hsp70 works

More information: Jiao Yang et al. Conformation transitions of the polypeptide-binding pocket support an active substrate release from Hsp70s, Nature Communications (2017). DOI: 10.1038/s41467-017-01310-z

Related Stories

Maximum precision in protein synthesis

September 8, 2017

Researchers from the Center for Molecular Biology of Heidelberg University (ZMBH) and the German Cancer Research Center (DKFZ) have investigated the mode of action of a molecular chaperone vital to protein synthesis. Together ...

Molecular chaperones help with folding

May 12, 2015

Chaperones are molecular helpers that assist other proteins with folding. One such chaperone is the so-called heat shock protein 60 (Hsp60). This protein forms structures in mitochondria that resemble barrels in which folding ...

Recommended for you

Insect antibiotic provides new way to eliminate bacteria

November 15, 2018

An antibiotic called thanatin attacks the way the outer membrane of Gram-negative bacteria is built. Researchers at the University of Zurich have now found that this happens through a previously unknown mechanism. Thanatin, ...

Why macrophages rest in healthy tissue

November 15, 2018

ETH scientists have shown that the immune system's macrophages are regulated not only biochemically, but mechanically as well. This could explain why the cells are less active in healthy body tissue.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.