Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Some degenerative diseases prove similar at the molecular level

07.05.2007
Alzheimer’s disease, Parkinson’s disease, type 2 diabetes, the human version of mad cow disease (Creutzfeldt-Jakob disease), and other degenerative diseases are more closely related at the molecular level than many scientists realized, an international team of researchers, including an ESRF researcher, report in the journal Nature.

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.

... more about:
»Amyloid »fibril »zipper

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
Further information:
http://www.esrf.fr/news/pressreleases/disease/

Further reports about: Amyloid fibril zipper

More articles from Life Sciences:

nachricht Climate Impact Research in Hannover: Small Plants against Large Waves
17.08.2018 | Leibniz Universität Hannover

nachricht First transcription atlas of all wheat genes expands prospects for research and cultivation
17.08.2018 | Leibniz-Institut für Pflanzengenetik und Kulturpflanzenforschung

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Color effects from transparent 3D-printed nanostructures

New design tool automatically creates nanostructure 3D-print templates for user-given colors
Scientists present work at prestigious SIGGRAPH conference

Most of the objects we see are colored by pigments, but using pigments has disadvantages: such colors can fade, industrial pigments are often toxic, and...

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...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

LaserForum 2018 deals with 3D production of components

17.08.2018 | 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

 
Latest News

Smallest transistor worldwide switches current with a single atom in solid electrolyte

17.08.2018 | Physics and Astronomy

Robots as Tools and Partners in Rehabilitation

17.08.2018 | Information Technology

Climate Impact Research in Hannover: Small Plants against Large Waves

17.08.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>