Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Unweaving amyloid fibers to solve prion puzzles

09.06.2005


Amyloid fibers are best known as the plaque that gunks up neurons in people with neurodegenerative illnesses such as Alzheimer’s and Creutzfeldt-Jacob disease--the human analog of mad cow disease. But even though amyloids are common and implicated in a host of conditions, researchers haven’t been able to identify their precise molecular structures. Conventional techniques used to image proteins, such as X-ray crystallography and nuclear magnetic resonance imaging, don’t work with fibrous structures such as amyloids. And scientists depend on these high resolution images of molecules in order to study their function.



Now, researchers have found a way to work around these limitations, illuminating the configuration of these sometimes pernicious molecules. And even though this work was done in yeast, the results provide hints as to why mad-cow type diseases tend to have a difficult time jumping species. "These findings give us some fundamental insights in how amyloid fibers form," says Whitehead Member Susan Lindquist, lead scientist in the research team whose results will be published in the June 9 issue of the journal Nature. "They solve the important problem of identifying the intermolecular contacts that hold the amyloid fiber together."

Amyloid fibers are often composed of prions--proteins that misfold and recruit neighboring proteins to misfold as well, a process that Lindquist calls a "conformational cascade." When such a cascade occurs, the prions join and form amyloid fibers. (While not all amyloids are composed of prions, all known prions, in their transmissible states, form amyloid fibers.) But still, many scientists have been frustrated by their inability to gain anything more than a limited understanding of an amyloid’s architecture.


Rajaraman Krishnan, a postdoctoral researcher in Lindquist’s lab, found a way around that problem using strains of yeast. Rather than develop a single high-tech method for solving the amyloid structure, he instead used a combination of low resolution tools to analyze varieties of prion strains and piece together the puzzle of how amyloids form. "We now have an overall picture of how prions join together to form the amyloid’s molecular structure," says Lindquist, who also is a professor of biology at MIT.

Prions are in the business of converting other prion molecules to join their ranks. And as they join together, they can create an amyloid fiber. To understand the nature of this fiber, it’s necessary to understand how the prions that comprise it attach to each other. Krishnan was able to identify the precise segment at which the prions interact--something that no one had done before him with a real prion.

To do this, Krishnan took a variety of yeast prion strains and modified them in such a way that if particular designated regions came into contact with each other, they would emit a fluorescent signal, allowing him to map the pattern by which the different strains of prions interacted with each other.

He found that each prion molecule had only two points at which they connected to other prion molecules. One point he called the "head," the other the "tail." The head of one prion would only interact with the head of another prion, and likewise with tails. Remarkably, the same prion from the same yeast species could sometimes fold differently, and this fold would form its own cascade of interactions. In this altered form, the prion molecules interact in slightly different places, presenting different surfaces to promote the conversion of other prion molecules.

Lindquist believes that the techniques used in this study will ultimately prove useful for studying prion strains found in mammals like mice, cows, and ultimately humans. "This gives us insight as to why some prions can’t cross the species barrier while others can--as they have with mad cows and humans.," says Lindquist. That gap has also been observed between other species, she notes: "In fact, some type of prions from infected hamsters can’t make the species jump into mice, while others do, and vice versa."

While the results of this research are clearly of interest to scientists investigating conditions such as Alzheimer’s, it’s also relevant to scientists studying nanotechnology. In March of 2003, Lindquist published a paper in the journal Proceedings of the National Academy of Sciences in which she described how amyloid fibers can become the core of nanoscale electrical wires, opening the possibility of one day incorporating them into integrated circuits.

"These findings are quite relevant for the material sciences," says Lindquist. "The more we understand about how these fibers work, the more we can get them to self-assemble," a key advantage for nanoscale devices that are very difficult to manipulate directly. In addition, amyloids are also unusually robust, which also makes them attractive for nano devices. The advantage of the yeast protein is that it is not toxic, even for yeast.

David Cameron | EurekAlert!
Further information:
http://www.wi.mit.edu

More articles from Life Sciences:

nachricht Nanoparticle Exposure Can Awaken Dormant Viruses in the Lungs
16.01.2017 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt

nachricht Cholera bacteria infect more effectively with a simple twist of shape
13.01.2017 | Princeton University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Designing Architecture with Solar Building Envelopes

Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.

As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...

Im Focus: How to inflate a hardened concrete shell with a weight of 80 t

At TU Wien, an alternative for resource intensive formwork for the construction of concrete domes was developed. It is now used in a test dome for the Austrian Federal Railways Infrastructure (ÖBB Infrastruktur).

Concrete shells are efficient structures, but not very resource efficient. The formwork for the construction of concrete domes alone requires a high amount of...

Im Focus: Bacterial Pac Man molecule snaps at sugar

Many pathogens use certain sugar compounds from their host to help conceal themselves against the immune system. Scientists at the University of Bonn have now, in cooperation with researchers at the University of York in the United Kingdom, analyzed the dynamics of a bacterial molecule that is involved in this process. They demonstrate that the protein grabs onto the sugar molecule with a Pac Man-like chewing motion and holds it until it can be used. Their results could help design therapeutics that could make the protein poorer at grabbing and holding and hence compromise the pathogen in the host. The study has now been published in “Biophysical Journal”.

The cells of the mouth, nose and intestinal mucosa produce large quantities of a chemical called sialic acid. Many bacteria possess a special transport system...

Im Focus: Newly proposed reference datasets improve weather satellite data quality

UMD, NOAA collaboration demonstrates suitability of in-orbit datasets for weather satellite calibration

"Traffic and weather, together on the hour!" blasts your local radio station, while your smartphone knows the weather halfway across the world. A network of...

Im Focus: Repairing defects in fiber-reinforced plastics more efficiently

Fiber-reinforced plastics (FRP) are frequently used in the aeronautic and automobile industry. However, the repair of workpieces made of these composite materials is often less profitable than exchanging the part. In order to increase the lifetime of FRP parts and to make them more eco-efficient, the Laser Zentrum Hannover e.V. (LZH) and the Apodius GmbH want to combine a new measuring device for fiber layer orientation with an innovative laser-based repair process.

Defects in FRP pieces may be production or operation-related. Whether or not repair is cost-effective depends on the geometry of the defective area, the tools...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

Nothing will happen without batteries making it happen!

05.01.2017 | Event News

 
Latest News

Multiregional brain on a chip

16.01.2017 | Power and Electrical Engineering

New technology enables 5-D imaging in live animals, humans

16.01.2017 | Information Technology

Researchers develop environmentally friendly soy air filter

16.01.2017 | Power and Electrical Engineering

VideoLinks
B2B-VideoLinks
More VideoLinks >>>