The brains of patients with these diseases contain harmful rope-like structures known as amyloid fibrils, which are protein molecules linked by water-tight “molecular zippers”.
“We have shown that the fibrils have a common atomic-level structure,” said David Eisenberg, a UCLA-DOE professor of chemistry and biology and a member of the research team. “All of these diseases are similar at the molecular level; all of them have a dry steric zipper. With each disease, a different protein transforms into amyloid fibrils, but the proteins are very similar at the atomic level.”
The UCLA team, together with scientists from the University of Copenhagen and the ESRF, carried out part of their research at the microfocus beamline at the ESRF, where they used a very small beam of X-rays to study micro-crystals. “It has been a great international collaboration,” Eisenberg said.
The research, while still preliminary, could help scientists develop tools for diagnosing these diseases, and potentially for treating them through “structure-based drug design,” said Eisenberg.
The researchers report 11 new three-dimensional structures of fibril forming segments, including those for both of the main proteins that form amyloid fibrils in Alzheimer’s disease.
“It has been a joy to see so many new structures,” said Michael Sawaya, member of the team. “We see many similarities, but some details are different. As we study more structures, we expect to determine the common features among them”.
“It is clear from the positions of the atoms where the zipper is,” Sawaya added. “Like pieces in a jigsaw puzzle, they have to fit together just right. We are finding out how they fit together. We don’t yet know all the ways of forming the zippers; we are working to fill in the missing pieces and are hopeful of doing so.”
The research shows that very short segments of proteins are involved in forming amyloid fibrils; Eisenberg and his colleagues know some of the segments. Knowing the segments makes it easier to design tests to detect whether a new drug is effective, Eisenberg noted. Several of the disease-related proteins contain more than one amyloid fibril-forming segment.
If the molecular zipper is universal in amyloid fibrils, as Eisenberg believes, is it possible to pry open the zipper or prevent its formation? The team can now produce fibrils and has developed a test to determine whether the fibrils break up, using a wide variety of chemical compounds. This strategy could be potentially used to break up the fibrils.
A mystery on which the new Nature paper sheds light is what causes different strains of prions (infectious proteins) in which the protein sequence is identical. Scientists present a strong hypothesis that the origin of prion strains is encoded in the packing of the molecules in the fibrils.
In an earlier Nature paper (9 June 2005), Eisenberg and his colleagues presented the three-dimensional structure of an amyloid-like protein from yeast that revealed the surprising molecular zipper.“In 2005, we were like prospectors who found flakes of gold in a stream,” Eisenberg said. “Now we see the real nuggets. In this paper, we present atomic-level structures for crystals related to fibrils from proteins associated with numerous human diseases.”
Montserrat Capellas | alfa
Nanoparticle Exposure Can Awaken Dormant Viruses in the Lungs
16.01.2017 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt
Cholera bacteria infect more effectively with a simple twist of shape
13.01.2017 | Princeton University
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...
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...
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...
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...
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...
10.01.2017 | Event News
09.01.2017 | Event News
05.01.2017 | Event News
16.01.2017 | Power and Electrical Engineering
16.01.2017 | Information Technology
16.01.2017 | Power and Electrical Engineering