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 Newly designed molecule binds nitrogen
23.02.2018 | Julius-Maximilians-Universität Würzburg

nachricht Atomic Design by Water
23.02.2018 | Max-Planck-Institut für Eisenforschung GmbH

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Attoseconds break into atomic interior

A newly developed laser technology has enabled physicists in the Laboratory for Attosecond Physics (jointly run by LMU Munich and the Max Planck Institute of Quantum Optics) to generate attosecond bursts of high-energy photons of unprecedented intensity. This has made it possible to observe the interaction of multiple photons in a single such pulse with electrons in the inner orbital shell of an atom.

In order to observe the ultrafast electron motion in the inner shells of atoms with short light pulses, the pulses must not only be ultrashort, but very...

Im Focus: Good vibrations feel the force

A group of researchers led by Andrea Cavalleri at the Max Planck Institute for Structure and Dynamics of Matter (MPSD) in Hamburg has demonstrated a new method enabling precise measurements of the interatomic forces that hold crystalline solids together. The paper Probing the Interatomic Potential of Solids by Strong-Field Nonlinear Phononics, published online in Nature, explains how a terahertz-frequency laser pulse can drive very large deformations of the crystal.

By measuring the highly unusual atomic trajectories under extreme electromagnetic transients, the MPSD group could reconstruct how rigid the atomic bonds are...

Im Focus: Developing reliable quantum computers

International research team makes important step on the path to solving certification problems

Quantum computers may one day solve algorithmic problems which even the biggest supercomputers today can’t manage. But how do you test a quantum computer to...

Im Focus: In best circles: First integrated circuit from self-assembled polymer

For the first time, a team of researchers at the Max-Planck Institute (MPI) for Polymer Research in Mainz, Germany, has succeeded in making an integrated circuit (IC) from just a monolayer of a semiconducting polymer via a bottom-up, self-assembly approach.

In the self-assembly process, the semiconducting polymer arranges itself into an ordered monolayer in a transistor. The transistors are binary switches used...

Im Focus: Demonstration of a single molecule piezoelectric effect

Breakthrough provides a new concept of the design of molecular motors, sensors and electricity generators at nanoscale

Researchers from the Institute of Organic Chemistry and Biochemistry of the CAS (IOCB Prague), Institute of Physics of the CAS (IP CAS) and Palacký University...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

2nd International Conference on High Temperature Shape Memory Alloys (HTSMAs)

15.02.2018 | Event News

Aachen DC Grid Summit 2018

13.02.2018 | Event News

How Global Climate Policy Can Learn from the Energy Transition

12.02.2018 | Event News

 
Latest News

Basque researchers turn light upside down

23.02.2018 | Physics and Astronomy

Finnish research group discovers a new immune system regulator

23.02.2018 | Health and Medicine

Attoseconds break into atomic interior

23.02.2018 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>