Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Researchers Gain Insight into Key Protein Linked to Development of Cancers and Neurodegenerative Disorders

31.05.2013
Virginia Commonwealth University researchers studying a key molecular player called Hsp70 that is responsible for protein homeostasis have uncovered how it binds together with another molecule responsible for intracellular energy transfer to enhance its overall activity and efficiency – details that have previously not been well understood.
Heat shock proteins, particularly the 70-kilodalton heat shock proteins, Hsp70, are important for cellular processes such as protein folding and protecting cells from stress. It is also involved with protein assembly, degradation and transport. Imbalances in protein homeostasis have been previously found to contribute to the onset of neurodegenerative diseases and cancers.

In the study, published this week in the Online First section of Nature Structural & Molecular Biology, a publication of the Nature journal family, researchers conducted a biochemical analysis of the structure to learn how ATP binding allosterically opens the polypeptide-binding site. In order for Hsp70 to do its job of regulating its binding to unfolded polypeptide substrates, it gains energy from the process of ATP hydrolysis. ATP is a molecule responsible for intracellular energy transfer.

The team found that when Hsp70 binds ATP it promotes the allosteric opening of the polypeptide binding site.

“Due to their essential roles in protein trafficking and proper folding since mis-folded proteins can disrupt cell function, Hsp70s are inextricably linked to the development of cancers, aging and neurodegenerative disorders,” said Qinglian Liu, Ph.D., assistant professor in the Department of Physiology and Biophysics in the VCU School of Medicine.

“Understanding the structural properties at the atomic level and molecular working of Hsp70s will pave the foundation for designing efficient and potent small molecule drugs to specifically modulate the function of Hsp70s. The small molecule drugs may become novel and efficient treatments for cancers or neurodegenerative disorders,” she said.

Liu said that the team’s structural and biochemical analysis revealed how Hsp70s use ATP to open their peptide substrate binding site and thus regulate their ability in binding peptide substrates.

“These findings help us understand at the atomic level how Hsp70s function in maintaining the well-being of cellular proteins, such as folding, assembly, transport and degradation,” said Liu.

According to Liu, future work will move the team in two directions. First, based on this published work, they aim to design specific and potent modulators for Hsp70s and test their potential in treating cancers or neurodegenerative disorders. A second focus will be to study how Hsp70s cooperate with their Hsp40 partners to achieve their optimum activity in maintaining protein homeostasis.

VCU collaborated with Brookhaven National Laboratory, the Department of Biochemistry and Molecular Biophysics at Columbia University in New York. All the work was conducted at VCU, with the exception of the X-ray diffraction data collection and analysis, which was done at Brookhaven’s National Synchrotron Light Source.

This work was supported by startup funds from the VCU School of Medicine, a New Scholar Award in Aging from the Ellison Medical Foundation, grant number AG-NS-0587-09, and a Grant-In-Aid Award from the American Heart Association, grant number 11GRNT7460003.

The study is titled “Allosteric opening of the polypeptide-binding site when an Hsp70 binds AT

Sathya Achia Abraham | EurekAlert!
Further information:
http://www.vcu.edu

More articles from Life Sciences:

nachricht Rutgers scientists discover 'Legos of life'
23.01.2018 | Rutgers University

nachricht Researchers identify a protein that keeps metastatic breast cancer cells dormant
23.01.2018 | Institute for Research in Biomedicine (IRB Barcelona)

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Optical Nanoscope Allows Imaging of Quantum Dots

Physicists have developed a technique based on optical microscopy that can be used to create images of atoms on the nanoscale. In particular, the new method allows the imaging of quantum dots in a semiconductor chip. Together with colleagues from the University of Bochum, scientists from the University of Basel’s Department of Physics and the Swiss Nanoscience Institute reported the findings in the journal Nature Photonics.

Microscopes allow us to see structures that are otherwise invisible to the human eye. However, conventional optical microscopes cannot be used to image...

Im Focus: Artificial agent designs quantum experiments

On the way to an intelligent laboratory, physicists from Innsbruck and Vienna present an artificial agent that autonomously designs quantum experiments. In initial experiments, the system has independently (re)discovered experimental techniques that are nowadays standard in modern quantum optical laboratories. This shows how machines could play a more creative role in research in the future.

We carry smartphones in our pockets, the streets are dotted with semi-autonomous cars, but in the research laboratory experiments are still being designed by...

Im Focus: Scientists decipher key principle behind reaction of metalloenzymes

So-called pre-distorted states accelerate photochemical reactions too

What enables electrons to be transferred swiftly, for example during photosynthesis? An interdisciplinary team of researchers has worked out the details of how...

Im Focus: The first precise measurement of a single molecule's effective charge

For the first time, scientists have precisely measured the effective electrical charge of a single molecule in solution. This fundamental insight of an SNSF Professor could also pave the way for future medical diagnostics.

Electrical charge is one of the key properties that allows molecules to interact. Life itself depends on this phenomenon: many biological processes involve...

Im Focus: Paradigm shift in Paris: Encouraging an holistic view of laser machining

At the JEC World Composite Show in Paris in March 2018, the Fraunhofer Institute for Laser Technology ILT will be focusing on the latest trends and innovations in laser machining of composites. Among other things, researchers at the booth shared with the Aachen Center for Integrative Lightweight Production (AZL) will demonstrate how lasers can be used for joining, structuring, cutting and drilling composite materials.

No other industry has attracted as much public attention to composite materials as the automotive industry, which along with the aerospace industry is a driver...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

10th International Symposium: “Advanced Battery Power – Kraftwerk Batterie” Münster, 10-11 April 2018

08.01.2018 | Event News

See, understand and experience the work of the future

11.12.2017 | Event News

Innovative strategies to tackle parasitic worms

08.12.2017 | Event News

 
Latest News

Rutgers scientists discover 'Legos of life'

23.01.2018 | Life Sciences

Seabed mining could destroy ecosystems

23.01.2018 | Earth Sciences

Transportable laser

23.01.2018 | Physics and Astronomy

VideoLinks Science & Research
Overview of more VideoLinks >>>