Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Fox Chase Cancer Center researcher develops new model for studying prions – mad cow disease

03.12.2003


Fox Chase Cancer Center researchers and their colleagues in Japan and San Francisco have obtained new insight into the molecular structure of prion particles responsible for mad cow disease and other degenerative neurological disorders. In new research to be published in this week’s Online Early Edition of the Proceedings of the National Academy of Sciences (www.pnas.org), Fox Chase biophysicist Heinrich Roder, Ph.D., and colleagues describe a computer model of the structural core of prions, based on biophysical measurements of a fibrous form of a prion protein fragment. Prions are infectious protein particles linked to degenerative neurological diseases in animals and humans, such as mad cow disease (bovine spongiform encephalopathy or BSE) in cattle, scrapie in sheep and goats, and Creutzfeldt-Jakob disease (CJD) in humans.



For proteins, form really does equal function. Not only are they essential building blocks of the body, but proteins are also the workers of every cell, carrying out its specific functions. This function depends on the ultimate three-dimensional shape of the protein, a form achieved by folding flexible chains of amino acids until each is properly aligned so that the protein can do its job. Normally, the folding of proteins is highly efficient and specific, but sometimes the process goes awry, resulting in dangerous misfolded forms.

Prion diseases result from the conversion of a normal cellular protein into an alternative structure that forms threadlike fibers called amyloid fibrils. They accumulate in target tissues, such as brain tissue, where they cause the progressive degeneration of cognitive and motor functions and ultimately prove fatal.


Amyloid fibrils form as a result of mistakes in a protein’s normal folding process. Each disease involving amyloid fibrils stems from the misfolding of a different protein that then packs into a similar structure. The formation of amyloid fibrils is linked to a wide range of diseases, not only BSE and CJD but also Alzheimer’s disease, Type II diabetes and Parkinson’s disease.

"Unraveling the molecular basis of this fundamental process is a necessary first step toward treating these diseases," Roder said. Unlike other amyloid fibrils, prion particles can interact with the normal host protein and transmit the disease from one individual to another. In some especially alarming cases, the disease can be transmitted from one species to another, as in the case of a new human variant of CJD linked to BSE.

"Despite the growing list of diseases known to involve deposits of fibrillar protein aggregates in and around cells, our understanding of the structural basis of these amyloid fibrils is rudimentary at best," said Roder. The large size and insolubility of these protein aggregates have limited the use of high-resolution techniques for structural studies, such as X-ray crystallography and nuclear magnetic resonance.

"We have been able to overcome some of these limitations by using NMR-based hydrogen-deuterium exchange experiments in conjunction with a solvent quenching protocol," Roder explained.

The new paper, entitled "NMR-Detected Hydrogen Exchange and Molecular Dynamics Simulations Provide Structural Insight into Fibril Formation of Prion Protein Fragment 106-126" will appear in the Dec. 9 issue of PNAS.

"Understanding the physical principles underlying the folding of proteins is a major challenge of molecular biophysics," said Roder. "Because aggregation of misfolded proteins can lead to disease, this basic knowledge has important implications for medicine as well as bioinformatics, biotechnology and cell biology."

Kazuo Kuwata, Ph.D., of the department of biochemistry and biophysics at Gifu University’s School of Medicine in Japan is also a corresponding author of the study and has been a visiting scientist in Roder’s Fox Chase laboratory. Other study authors include staff scientist Hong Cheng, Ph.D., of Roder’s lab; Thomas L. James, Ph.D., of the department of pharmaceutical chemistry at the University of California at San Francisco; and Tomoharu Matumoto, Ph.D., and Kuniaki Nagayama, Ph.D., of the laboratory of ultrastructure research at Japan’s National Institute for Physiologic Sciences.


Fox Chase Cancer Center, one of the nation’s first comprehensive cancer centers designated by the National Cancer Institute in 1974, conducts basic, clinical, population and translational research; programs of prevention, detection and treatment of cancer; and community outreach. For more information about Fox Chase activities, visit the Center’s web site at www.fccc.edu or call 1-888-FOX CHASE.

Karen Carter Mallet | EurekAlert!
Further information:
http://www.fccc.edu/
http://www.pnas.org

More articles from Life Sciences:

nachricht Could this protein protect people against coronary artery disease?
17.11.2017 | University of North Carolina Health Care

nachricht Microbial resident enables beetles to feed on a leafy diet
17.11.2017 | Max-Planck-Institut für chemische Ökologie

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: A “cosmic snake” reveals the structure of remote galaxies

The formation of stars in distant galaxies is still largely unexplored. For the first time, astron-omers at the University of Geneva have now been able to closely observe a star system six billion light-years away. In doing so, they are confirming earlier simulations made by the University of Zurich. One special effect is made possible by the multiple reflections of images that run through the cosmos like a snake.

Today, astronomers have a pretty accurate idea of how stars were formed in the recent cosmic past. But do these laws also apply to older galaxies? For around a...

Im Focus: Visual intelligence is not the same as IQ

Just because someone is smart and well-motivated doesn't mean he or she can learn the visual skills needed to excel at tasks like matching fingerprints, interpreting medical X-rays, keeping track of aircraft on radar displays or forensic face matching.

That is the implication of a new study which shows for the first time that there is a broad range of differences in people's visual ability and that these...

Im Focus: Novel Nano-CT device creates high-resolution 3D-X-rays of tiny velvet worm legs

Computer Tomography (CT) is a standard procedure in hospitals, but so far, the technology has not been suitable for imaging extremely small objects. In PNAS, a team from the Technical University of Munich (TUM) describes a Nano-CT device that creates three-dimensional x-ray images at resolutions up to 100 nanometers. The first test application: Together with colleagues from the University of Kassel and Helmholtz-Zentrum Geesthacht the researchers analyzed the locomotory system of a velvet worm.

During a CT analysis, the object under investigation is x-rayed and a detector measures the respective amount of radiation absorbed from various angles....

Im Focus: Researchers Develop Data Bus for Quantum Computer

The quantum world is fragile; error correction codes are needed to protect the information stored in a quantum object from the deteriorating effects of noise. Quantum physicists in Innsbruck have developed a protocol to pass quantum information between differently encoded building blocks of a future quantum computer, such as processors and memories. Scientists may use this protocol in the future to build a data bus for quantum computers. The researchers have published their work in the journal Nature Communications.

Future quantum computers will be able to solve problems where conventional computers fail today. We are still far away from any large-scale implementation,...

Im Focus: Wrinkles give heat a jolt in pillared graphene

Rice University researchers test 3-D carbon nanostructures' thermal transport abilities

Pillared graphene would transfer heat better if the theoretical material had a few asymmetric junctions that caused wrinkles, according to Rice University...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Ecology Across Borders: International conference brings together 1,500 ecologists

15.11.2017 | Event News

Road into laboratory: Users discuss biaxial fatigue-testing for car and truck wheel

15.11.2017 | Event News

#Berlin5GWeek: The right network for Industry 4.0

30.10.2017 | Event News

 
Latest News

NASA detects solar flare pulses at Sun and Earth

17.11.2017 | Physics and Astronomy

NIST scientists discover how to switch liver cancer cell growth from 2-D to 3-D structures

17.11.2017 | Health and Medicine

The importance of biodiversity in forests could increase due to climate change

17.11.2017 | Studies and Analyses

VideoLinks
B2B-VideoLinks
More VideoLinks >>>