Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

First direct information about the prion¹s molecular structure reported

06.10.2009
A collaboration between scientists at Vanderbilt University and the University of California, San Francisco has led to the first direct information about the molecular structure of prions.

­In addition, the study has revealed surprisingly large structural differences between natural prions and the closest synthetic analogs that scientists have created in the lab.

Prions are the infectious proteins responsible for human Creutzfeldt-Jakob disease, bovine spongiform encephalopathy, or ³mad cow² disease, scrapie in sheep and several other related nervous system disorders in mammals. For a number of years, scientists have been using the tools of genetic engineering to create synthetic versions of these particles so they could study them more easily. Although researchers have made particles that appear identical to natural prions, they have had trouble duplicating their infectious behavior.

³We expected to find subtle differences, but we found major differences instead,² said Gerald Stubbs, professor of biological sciences at Vanderbilt University. ³Although we cannot say for certain that the differences we¹ve seen can explain why natural prions are so infectious, there is a good chance that they are closely related.²

The study, which was published online in the Proceedings of the National Academy of Sciences last week, was a joint effort of the Stubbs laboratory and that of Stanley Prusiner at the University of California, San Francisco, who received the Nobel prize for the discovery of prions.

³Our results will aid in attempts to create the infectious synthetic prions that are needed to figure out how prions work and ultimately to find cures for the diseases that they cause,² said the lead author of the study, Holger Wille, assistant adjunct professor of neurology in the Institute for Neurodegenerative Diseases, which is based at UCSF and directed by Prusiner.

Prusiner¹s group was the first one that succeeded in making infectious prions in the test tube. However, they are not nearly as infectious as the real thing. Six years ago, Prusiner contacted Stubbs, who is a world authority on determining the molecular structures of fibrous materials, and asked if he was interested in collaborating on an effort to characterize the detailed structure of prions. It didn¹t take much convincing. ³I¹ve always been interested in prions, so I readily agreed,² said Stubbs.

Prions, because of their association with mad cow disease, are the most notorious of the amyloids, which are insoluble clumps of fibrous protein that play a role in a number of neurodegenerative diseases, including Alzheimer¹s, Parkinson¹s and Lou Gehrig disease, as well as some other common illnesses, including type II diabetes. ³It is particularly difficult to determine the molecular structure of fibrous materials like these because they have an intrinsically high level of disorder,² Stubbs explained.

When viewed with an electron microscope, which can magnify images up to one million times, the natural and synthetic prions look nearly identical. They both clump together to form microscopic filaments. At a magnification of approximately one hundred thousand times, the only visible difference is the width of the filaments: the synthetic material shows a wider distribution of widths than the natural material.

The Stubbs lab used unconventional X-ray diffraction methods to get the first details of the molecular structures of natural prions and Prusiner¹s synthetic prions. The researchers found that the synthetic prions were shaped something like a ladder. Based on electron microscopic images, the Prusiner lab had proposed that the natural prions have a more complex, three-sided cylindrical shape, and the X-ray experiments supported this proposal.

³The natural, infectious prions are folded into a much more complicated shape,² said Stubbs. Proteins are molecules that are folded into shapes that determine their biological properties. Prions and the other amyloids are cases in which proteins are misfolded into shapes that interfere with normal biological processes. ³Normally, the cellular systems deal with misfolded proteins but, for some reason, these slip through the cracks,² he said.

Prions don¹t have any DNA in their make-up so they don¹t reproduce in a normal fashion. Instead, they spread by transforming proteins they come into contact with into prions by causing them to misfold.

³Our data on prion structure is an important step toward understanding prion infection,² said Stubbs, ³and understanding the process is essential before people can design drugs that restrict or prevent it.² The research was supported by grants from the National Institutes of Health, Fairchild Foundation, G. Harold and Leila Y. Mathers Foundation, the National Science Foundation and the U.S. Department of Energy.

For more news about Vanderbilt, visit the Vanderbilt News Service homepage on the Internet at www.vanderbilt.edu/News.

UCSF is a leading university dedicated to promoting health worldwide through advanced biomedical research, graduate-level education in the life sciences and health professions, and excellence in patient care.

David F. Salisbury | Vanderbilt University
Further information:
http://www.vanderbilt.edu/News

More articles from Life Sciences:

nachricht Seeing on the Quick: New Insights into Active Vision in the Brain
15.08.2018 | Eberhard Karls Universität Tübingen

nachricht New Approach to Treating Chronic Itch
15.08.2018 | Universität Zürich

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Unraveling the nature of 'whistlers' from space in the lab

A new study sheds light on how ultralow frequency radio waves and plasmas interact

Scientists at the University of California, Los Angeles present new research on a curious cosmic phenomenon known as "whistlers" -- very low frequency packets...

Im Focus: New interactive machine learning tool makes car designs more aerodynamic

Scientists develop first tool to use machine learning methods to compute flow around interactively designable 3D objects. Tool will be presented at this year’s prestigious SIGGRAPH conference.

When engineers or designers want to test the aerodynamic properties of the newly designed shape of a car, airplane, or other object, they would normally model...

Im Focus: Robots as 'pump attendants': TU Graz develops robot-controlled rapid charging system for e-vehicles

Researchers from TU Graz and their industry partners have unveiled a world first: the prototype of a robot-controlled, high-speed combined charging system (CCS) for electric vehicles that enables series charging of cars in various parking positions.

Global demand for electric vehicles is forecast to rise sharply: by 2025, the number of new vehicle registrations is expected to reach 25 million per year....

Im Focus: The “TRiC” to folding actin

Proteins must be folded correctly to fulfill their molecular functions in cells. Molecular assistants called chaperones help proteins exploit their inbuilt folding potential and reach the correct three-dimensional structure. Researchers at the Max Planck Institute of Biochemistry (MPIB) have demonstrated that actin, the most abundant protein in higher developed cells, does not have the inbuilt potential to fold and instead requires special assistance to fold into its active state. The chaperone TRiC uses a previously undescribed mechanism to perform actin folding. The study was recently published in the journal Cell.

Actin is the most abundant protein in highly developed cells and has diverse functions in processes like cell stabilization, cell division and muscle...

Im Focus: Lining up surprising behaviors of superconductor with one of the world's strongest magnets

Scientists have discovered that the electrical resistance of a copper-oxide compound depends on the magnetic field in a very unusual way -- a finding that could help direct the search for materials that can perfectly conduct electricity at room temperatur

What happens when really powerful magnets--capable of producing magnetic fields nearly two million times stronger than Earth's--are applied to materials that...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Within reach of the Universe

08.08.2018 | Event News

A journey through the history of microscopy – new exhibition opens at the MDC

27.07.2018 | Event News

2018 Work Research Conference

25.07.2018 | Event News

 
Latest News

Unraveling the nature of 'whistlers' from space in the lab

15.08.2018 | Physics and Astronomy

Diving robots find Antarctic winter seas exhale surprising amounts of carbon dioxide

15.08.2018 | Earth Sciences

Early opaque universe linked to galaxy scarcity

15.08.2018 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>