Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Marking Folded Proteins for Basic Alzheimer’s Studies

21.10.2008
Biochemists Lila Gierasch and Beena Krishnan at the University of Massachusetts Amherst have found a way to slip a fluorescent marker into one of a cell’s molecular machines so it lights up when it has formed the proper shape to carry out the cell’s “work orders.”

The new technique should allow labeling of correctly folded proteins in a living cell or similar natural environment to study the origins of protein-misfolding diseases such as cystic fibrosis, Alzheimer’s and Parkinson’s.

Findings of Gierasch, a distinguished professor of biochemistry and molecular biology, and Beena Krishnan, a postdoctoral fellow, appear today in the journal, Chemistry and Biology.

Cells, once thought to be simple watery bags, are now understood to be more like a thick porridge of protein chains, nucleic acids, membranes and other components. This makes it extremely difficult to observe the delicate protein-folding process, according to Gierasch, who says it’s like trying to watch knot-tying in a microscopic bowl of spaghetti. By discovering how to mark certain protein segments with naturally fitting fluorescent inserts, she and Krishnan have created what they call a “structure sensor.” It lights up only when the protein is perfectly folded, allowing it to be seen against the background of cellular complexity.

Proteins carry out thousands of normal cell operations by folding themselves into different three-dimensional, origami-like shapes matched to a single job as a key fits a lock. It’s believed that misfolding occurs regularly and when a cell detects mistakes, it just recycles protein parts and uses them again. However, if a certain misfolded key somehow gets past the cell’s “quality control,” Gierasch notes, proteins may aggregate or clump, with devastating results that include neurodegenerative diseases and other pathologies.

Fluorescent marking isn’t a new technique, but Gierasch and Krishnan applied it in a new way, snipping a segment of naturally occurring protein and replacing it with what they dub a “cross-strand tetra-Cys motif.” When the two parts of the motif settle near each other when properly folded, the dye binds and gives off light. Interestingly, the FlAsH dye Krishnan and Gierasch used was developed by Roger Tsien, winner of the recently announced 2008 Nobel Prize in chemistry.

Medical researchers around the world who use the new method will be able to set up a series of protein-folding experiments. By varying factors in each experiment and using the “structure sensor” to check results, they’ll piece together how protein misfolding leads to disease.

“We took on the challenge in 2004 to look for a way to see a protein inside a living cell and watch as it folds without interfering with the natural process,” Gierasch notes. Their laboratory is one of only a handful around the country working on the problem. “Clinical researchers know that you can get sick from mistakes in folding, but we don’t know how, because until now we couldn’t begin to watch the correct cascade or pinpoint mistakes in it, in order to understand the illness.” In 2006, Gierasch received a National Institutes of Health Director’s Pioneer Award of $2.5 million for her research on protein folding in the cell.

Lila Gierasch | Newswise Science News
Further information:
http://www.umass.edu

More articles from Life Sciences:

nachricht Molecular libraries for organic light-emitting diodes
24.04.2017 | Goethe-Universität Frankfurt am Main

nachricht Fine organic particles in the atmosphere are more often solid glass beads than liquid oil droplets
21.04.2017 | Max-Planck-Institut für Chemie

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Making lightweight construction suitable for series production

More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.

Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...

Im Focus: Wonder material? Novel nanotube structure strengthens thin films for flexible electronics

Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.

"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...

Im Focus: Deep inside Galaxy M87

The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.

Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...

Im Focus: A Quantum Low Pass for Photons

Physicists in Garching observe novel quantum effect that limits the number of emitted photons.

The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...

Im Focus: Microprocessors based on a layer of just three atoms

Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.

Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Expert meeting “Health Business Connect” will connect international medical technology companies

20.04.2017 | Event News

Wenn der Computer das Gehirn austrickst

18.04.2017 | Event News

7th International Conference on Crystalline Silicon Photovoltaics in Freiburg on April 3-5, 2017

03.04.2017 | Event News

 
Latest News

Molecular libraries for organic light-emitting diodes

24.04.2017 | Life Sciences

Research sheds new light on forces that threaten sensitive coastlines

24.04.2017 | Earth Sciences

Making lightweight construction suitable for series production

24.04.2017 | Machine Engineering

VideoLinks
B2B-VideoLinks
More VideoLinks >>>