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 What happens in the cell nucleus after fertilization
06.12.2016 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt

nachricht Researchers uncover protein-based “cancer signature”
05.12.2016 | Universität Basel

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Significantly more productivity in USP lasers

In recent years, lasers with ultrashort pulses (USP) down to the femtosecond range have become established on an industrial scale. They could advance some applications with the much-lauded “cold ablation” – if that meant they would then achieve more throughput. A new generation of process engineering that will address this issue in particular will be discussed at the “4th UKP Workshop – Ultrafast Laser Technology” in April 2017.

Even back in the 1990s, scientists were comparing materials processing with nanosecond, picosecond and femtosesecond pulses. The result was surprising:...

Im Focus: Shape matters when light meets atom

Mapping the interaction of a single atom with a single photon may inform design of quantum devices

Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

Im Focus: MADMAX: Max Planck Institute for Physics takes up axion research

The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.

The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

Simple processing technique could cut cost of organic PV and wearable electronics

06.12.2016 | Materials Sciences

3-D printed kidney phantoms aid nuclear medicine dosing calibration

06.12.2016 | Medical Engineering

Robot on demand: Mobile machining of aircraft components with high precision

06.12.2016 | Power and Electrical Engineering

VideoLinks
B2B-VideoLinks
More VideoLinks >>>