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
Unique genome architectures after fertilisation in single-cell embryos
30.03.2017 | IMBA - Institut für Molekulare Biotechnologie der Österreichischen Akademie der Wissenschaften GmbH
Transport of molecular motors into cilia
28.03.2017 | Aarhus University
The Institute of Semiconductor Technology and the Institute of Physical and Theoretical Chemistry, both members of the Laboratory for Emerging Nanometrology (LENA), at Technische Universität Braunschweig are partners in a new European research project entitled ChipScope, which aims to develop a completely new and extremely small optical microscope capable of observing the interior of living cells in real time. A consortium of 7 partners from 5 countries will tackle this issue with very ambitious objectives during a four-year research program.
To demonstrate the usefulness of this new scientific tool, at the end of the project the developed chip-sized microscope will be used to observe in real-time...
Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.
The results will be published on March 22 in the journal „Astronomy & Astrophysics“.
Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...
Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.
Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...
In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...
20.03.2017 | Event News
14.03.2017 | Event News
07.03.2017 | Event News
30.03.2017 | Health and Medicine
30.03.2017 | Health and Medicine
30.03.2017 | Medical Engineering