Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Now researchers can see how unfolded proteins move in the cell

10.12.2014

When a large protein unfolds in transit through a cell, it slows down and can get stuck in traffic. Using a specialized microscope -- a sort of cellular traffic camera -- University of Illinois chemists now can watch the way the unfolded protein diffuses.

Studying the relationship between protein folding and transport could provide great insight into protein-misfolding diseases such as Alzheimer’s and Huntington’s. Chemistry professor Martin Gruebele and graduate students Minghao Guo and Hannah Gelman published their findings in the journal PLOS ONE.


By looking at the dynamics of how the unfolded protein moved in the cell (A), the researchers mapped areas in the cell with different rates of diffusion (B and C). | Photo courtesy Hannah Gelman

“We’re looking at the earliest stages of disease, the initial phases of transport of bad proteins,” Gruebele said. In the past, he said, much research on Alzheimer’s and similar disease focused on fibrils, large bundles of misfolded proteins that form in the brain.

“But now, we think the fibrils are just an end product that’s left over when the cell dies, and the actual killing mechanism has to do with migration of the protein to specific places in the cell like the outer membrane,” he said. “Understanding how these mechanisms work at a fundamental level is going to give people more handles on where to look to cure things.”

Researchers have hypothesized that an unfolded protein moves more slowly through the cell, because it would be a big, stringy mess rather than a tightly wrapped package. The Illinois team devised a way to measure how diffusion slows down when a protein unfolds using a fluorescence microscope, then used three-dimensional diffusion models to connect the protein’s unfolding to its motion.

The researchers found that the unfolded protein did indeed slow down, although its speed was not steady. It sometimes zoomed swiftly to a new location, and sometimes sat idling in one area, like a vehicle in stop-and-go rush-hour traffic. They were able to map out areas of the cell with different rates of diffusion, the cellular version of a speed limit.

The unfolded protein’s slowdown is not only due to size, however. The researchers did additional experiments to prove that the unfolded protein stuck to other molecules in the cell. A class of molecules in the cell called chaperones have the job of binding to parts of proteins that come unfolded, and the researchers found that the unfolded protein interacted more with chaperones than did the properly folded protein. However, when high numbers of proteins unfold, the cell’s systems can get overloaded and the chaperones can’t handle them all.

“Looking at something like this can start to give people a handle on why something that seems relatively harmless in vitro sometimes can have such a large effect in the cell,” Gelman said. “A change that makes a slightly less effective protein in the test tube can turn into a completely fatal mutation in the cell. First, the protein’s role in the cell can no longer be fulfilled. Second, as more and more unfold, they can disrupt the function of the whole cell.”

The researchers think that the unfolded protein is likely to stick to nonchaperone molecules, as well, causing other problems in the cell and disrupting the flow within a cell. They plan to use the specialized microscope to study other proteins and how unfolding affects their diffusion, to see if the properties they observed are universal or if each protein has its own response.

They also hope to use their method to watch how unfolded or misfolded proteins move to the cell’s membrane, where they aggregate and create the problems seen in Alzheimer’s and other diseases.

“There’s a whole cascade of things,” Gruebele said. “If you have a single car accident in the middle of nowhere, it’s really only a problem for the owner. But if you have a single car that stops in the middle of the road on the freeway in Los Angeles, very soon the entire freeway is going to be backed up. What we’re looking at is like the car stopping on the freeway. We’re not worried yet about what happens to the line of cars an hour later – that’s the fibril.”

The National Science Foundation supported this work.

Editor's note: To reach Martin Gruebele, call 217-333-1624; email: gruebele@scs.illinois.edu.

The paper, “Coupled Protein Diffusion and Folding in the Cell,” is available online.

Liz Ahlberg | University of Illinois
Further information:
http://news.illinois.edu/news/14/1209protein_unfolding_MarstinGruebele.html

More articles from Life Sciences:

nachricht How brains surrender to sleep
23.06.2017 | IMP - Forschungsinstitut für Molekulare Pathologie GmbH

nachricht A new technique isolates neuronal activity during memory consolidation
22.06.2017 | Spanish National Research Council (CSIC)

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Can we see monkeys from space? Emerging technologies to map biodiversity

An international team of scientists has proposed a new multi-disciplinary approach in which an array of new technologies will allow us to map biodiversity and the risks that wildlife is facing at the scale of whole landscapes. The findings are published in Nature Ecology and Evolution. This international research is led by the Kunming Institute of Zoology from China, University of East Anglia, University of Leicester and the Leibniz Institute for Zoo and Wildlife Research.

Using a combination of satellite and ground data, the team proposes that it is now possible to map biodiversity with an accuracy that has not been previously...

Im Focus: Climate satellite: Tracking methane with robust laser technology

Heatwaves in the Arctic, longer periods of vegetation in Europe, severe floods in West Africa – starting in 2021, scientists want to explore the emissions of the greenhouse gas methane with the German-French satellite MERLIN. This is made possible by a new robust laser system of the Fraunhofer Institute for Laser Technology ILT in Aachen, which achieves unprecedented measurement accuracy.

Methane is primarily the result of the decomposition of organic matter. The gas has a 25 times greater warming potential than carbon dioxide, but is not as...

Im Focus: How protons move through a fuel cell

Hydrogen is regarded as the energy source of the future: It is produced with solar power and can be used to generate heat and electricity in fuel cells. Empa researchers have now succeeded in decoding the movement of hydrogen ions in crystals – a key step towards more efficient energy conversion in the hydrogen industry of tomorrow.

As charge carriers, electrons and ions play the leading role in electrochemical energy storage devices and converters such as batteries and fuel cells. Proton...

Im Focus: A unique data centre for cosmological simulations

Scientists from the Excellence Cluster Universe at the Ludwig-Maximilians-Universität Munich have establised "Cosmowebportal", a unique data centre for cosmological simulations located at the Leibniz Supercomputing Centre (LRZ) of the Bavarian Academy of Sciences. The complete results of a series of large hydrodynamical cosmological simulations are available, with data volumes typically exceeding several hundred terabytes. Scientists worldwide can interactively explore these complex simulations via a web interface and directly access the results.

With current telescopes, scientists can observe our Universe’s galaxies and galaxy clusters and their distribution along an invisible cosmic web. From the...

Im Focus: Scientists develop molecular thermometer for contactless measurement using infrared light

Temperature measurements possible even on the smallest scale / Molecular ruby for use in material sciences, biology, and medicine

Chemists at Johannes Gutenberg University Mainz (JGU) in cooperation with researchers of the German Federal Institute for Materials Research and Testing (BAM)...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Plants are networkers

19.06.2017 | Event News

Digital Survival Training for Executives

13.06.2017 | Event News

Global Learning Council Summit 2017

13.06.2017 | Event News

 
Latest News

Quantum thermometer or optical refrigerator?

23.06.2017 | Physics and Astronomy

A 100-year-old physics problem has been solved at EPFL

23.06.2017 | Physics and Astronomy

Equipping form with function

23.06.2017 | Information Technology

VideoLinks
B2B-VideoLinks
More VideoLinks >>>