Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

How Copper Folds Protein into Parkinson's Plaques

15.06.2011
Researchers at North Carolina State University have figured out how copper induces misfolding in the protein associated with Parkinson’s disease, leading to creation of the fibrillar plaques which characterize the disease. This finding has implications for both the study of Parkinson’s progression, as well as for future treatments.

The protein in question, alpha-synuclein, is the major component of fibrillar plaques found in Parkinson’s patients. Researchers had already discovered that certain metals, including copper, could increase the rate of misfolding by binding with the protein, but were unsure of the mechanism by which this binding took place.

“We knew that the copper was interacting with a certain section of the protein, but we didn’t have a model for what was happening on the atomic level,” says Frisco Rose, Ph.D. candidate in physics and lead author of the paper describing the research. “Think of a huge swing set, with kids all swinging and holding hands – that’s the protein. Copper is a kid who wants a swing. There are a number of ways that copper could grab a swing, or bind to the protein, and each of those ways would affect all of the other kids on the swing set differently. We wanted to find the specific binding process that leads to misfolding.”

Rose and NC State colleagues Dr. Miroslav Hodak, research assistant professor of physics, and Dr. Jerzy Bernholc, Drexel Professor of Physics and Director of the Center for High Performance Simulation, developed a series of computer simulations designed to ferret out the most likely binding scenario.

According to Hodak, “We simulated the interactions of hundreds of thousands of atoms, which required multiple hundred thousand CPU-hour runs to study the onset of misfolding and the dynamics of the partially misfolded structures."

The number of calculations was so large that Hodak and Bernholc had to devise a new method to make it possible for a computer to process them. Only supercomputers like Jaguar, Oak Ridge National Laboratory’s most powerful supercomputer – the most powerful in the United States, in fact – were up to the task. But the simulations finally revealed the binding configuration most likely to result in misfolding.

Their results appear in the June 14 edition of Nature Scientific Reports.

The researchers hope that their finding will advance our understanding of Parkinson’s, one of the most common – and devastating – neurological diseases. “Understanding the molecular mechanism of Parkinson's disease should help researchers in developing drugs that treat the disease rather than merely alleviate symptoms," Bernholc says.

The research was funded by the Department of Energy and the National Science Foundation. The Department of Physics is part of NC State’s College of Physical and Mathematical Sciences.

Note to editors: An abstract of the paper follows.

“Mechanism of copper(II)-induced misfolding of Parkinson’s disease protein”

Authors: Frisco Rose, Miroslav Hodak, Jerzy Bernholc, North Carolina State University

Published: June 14, 2011 in Nature Scientific Reports

Abstract:
á-synuclein (áS) is a natively unfolded pre-synaptic protein found in all Parkinson’s disease patients as the major component of fibrillar plaques. Metal ions, and especially Cu(II), have been demonstrated to accelerate aggregation of áS into fibrillar plaques, the precursors to Lewy bodies. In this work, copper binding to áS is investigated by a combination of quantum and molecular mechanics simulations. Starting from the experimentally observed attachment site, several optimized structures of Cu-binding geometries are examined. The most energetically favorable attachment results in significant allosteric changes, making áS more susceptible to misfolding. Indeed, an inverse kinematics investigation of the configuration space uncovers a dynamically stable â-sheet conformation of Cu-áS that serves as a nucleation point for a second â-strand. Based on these findings, we propose an atomistic mechanism of copper-induced misfolding of áS as an initial event in the formation of Lewy bodies and thus in PD pathogenesis.

Tracey Peake | Newswise Science News
Further information:
http://www.ncsu.edu

More articles from Life Sciences:

nachricht Transport of molecular motors into cilia
28.03.2017 | Aarhus University

nachricht Asian dust providing key nutrients for California's giant sequoias
28.03.2017 | University of California - Riverside

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: A Challenging European Research Project to Develop New Tiny Microscopes

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...

Im Focus: Giant Magnetic Fields in the Universe

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...

Im Focus: Tracing down linear ubiquitination

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...

Im Focus: Perovskite edges can be tuned for optoelectronic performance

Layered 2D material improves efficiency for solar cells and LEDs

In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...

Im Focus: Polymer-coated silicon nanosheets as alternative to graphene: A perfect team for nanoelectronics

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...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

International Land Use Symposium ILUS 2017: Call for Abstracts and Registration open

20.03.2017 | Event News

CONNECT 2017: International congress on connective tissue

14.03.2017 | Event News

ICTM Conference: Turbine Construction between Big Data and Additive Manufacturing

07.03.2017 | Event News

 
Latest News

Transport of molecular motors into cilia

28.03.2017 | Life Sciences

A novel hybrid UAV that may change the way people operate drones

28.03.2017 | Information Technology

NASA spacecraft investigate clues in radiation belts

28.03.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>