Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

A quick-change artist: tiny protein folds faster than any other

18.10.2002


The world speed record for protein folding apparently goes to an unusually tiny specimen that traces its origins to Gila monster spit.


University of Florida researchers have discovered that the Tryptophan cage protein, derived from the saliva of the Gila monster lizard, zooms to its folded state, above, in four millionths of a second - about four times faster than any protein previously measured. The finding adds to the emerging knowledge about how proteins fold, information that could lead to better drugs and cures for diseases tied to misshapen proteins, such as Alzheimer’s, Parkinson’s and Mad Cow diseases.



So reports a team of University of Florida researchers in a paper published this week in the online edition of the Journal of the American Chemical Society. Though significant mainly from a purely scientific standpoint, the finding eventually may be important in researchers’ understanding of the underlying causes behind a host of maladies.

Proteins acquire their three-dimensional, blob-like shapes when the amino acids they are composed of spontaneously fold into place. The process has become a hot topic in science in recent years because the shape of proteins is directly tied to their function in the cells of animals and people. Misshapen proteins, or proteins whose amino acids form an even slightly different configuration than normal proteins, have been connected to Alzheimer’s disease and a range of other serious disorders.


The UF team found the protein Tryptophan cage, or Trp-cage for short, rockets from its two-dimensional, line-like state of 20 amino acids to its three-dimensional state in four-millionths of a second. That’s the fastest rate yet observed for a complete protein - and about four times faster than any other protein yet measured, UF researchers say.

With about 10 atoms per amino acid, the protein is composed of about 200 atoms, and each atom must interact with every other atom before finding its proper place in the structure. That means at least 40,000 atomic interactions - pushing and pulling movements - occur in an almost imperceptible period, said Stephen Hagen, an assistant professor of physics and one of the paper’s four UF authors.

“The fact that some proteins can fold incredibly fast is really a remarkable thing,” he said. “What is it that’s special about these molecules that enables them to solve a very difficult computational problem spontaneously in such a short amount of time?”

Vijay Pande, an assistant professor of chemistry at Stanford University, called the UF finding “really important and very exciting.” He said it could speed up biologists’ efforts to simulate the protein-folding process, which could lead to better drugs and cures for diseases tied to misshapen proteins.

Scientists have long known that instructions in genes’ DNA determine the amino acid code for proteins. However, they still don’t know the structure of most human proteins or the role they play in many inherited traits or diseases. The way amino acids come together to form proteins is one area researchers are plumbing for answers.

Enter the Gila monster. Trp-cage stems from a protein another group of researchers removed from the lizard’s saliva in an effort to understand why its bite makes some people ill but not others, said Adrian Roitberg, a UF assistant professor of chemistry. The researchers modified the protein’s structure to make it more stable and easier to work with, and then published the results of their work online, where the UF scientists learned about them.

With other proteins composed of hundreds or thousands of amino acids, Trp-cage’s small size might seem to explain its fast-folding speed, but protein size and speed are not related, Hagen said. More interestingly, researchers expected Trp-cage would fold at least 1,000 times slower than it does, leaving its blinding speed “quite a mystery,” Hagen said.

There are two ways of probing how proteins attain their shape: experiments in the lab and computer simulations. UF researchers have done both with Trp-cage.

Hagen’s team, which included Roitberg and UF physics doctoral students Linlin Qiu and Suzette Pabit, used an advanced instrument called a laser temperature jump spectrometer to observe and time Trp-cage’s transition from its unfolded to its folded state. Roitberg also was part of a separate team collaborating with researchers from the State University of New York-Stonybrook that simulated Trp-cage’s structure on a computer based solely on its amino acid code. The results, reported last month in the Journal of the American Chemical Society, caused a stir in the scientific community because the simulated Trp-cage was extremely close in size and shape to that of the actual observed protein.

If such a computational method ever could be used to replicate larger, more-complex human proteins, it could speed the pace of research dramatically because the laboratory experimental approach is difficult, time consuming and expensive, Roitberg and Hagen said. For now, however, such a goal is far off, because computers are not yet powerful enough to quickly process all the information about each atom’s forces on all of the other atoms in larger proteins.

Roitberg’s team’s simulation of tiny Trp-cage required 16 computers and three weeks of computing time - another indication of the protein’s speedy folding rate. Although protein fragments have been observed to fold faster, the complete Trp-cage is one of a kind. “Here’s a molecule that is able to do in four microseconds what it takes these computers several weeks to do,” Hagen said.

Hagen said many diseases are tied to misshapen proteins. These include Alzheimer’s, Parkinson’s disease, Mad Cow Disease and others, Pande said. For biomedical researchers interested in genetic therapy to correct these proteins’ shapes, that naturally raises the question of how proteins mis-fold into botched versions. So while the news about Trp-cage’s folding pace has no immediate biomedical application, it contributes to increasing knowledge about this important process, Hagen said.

Stephen Hagen | EurekAlert!
Further information:
http://www.ufl.edu/

More articles from Life Sciences:

nachricht Building a brain, cell by cell: Researchers make a mini neuron network (of two)
23.05.2018 | Institute of Industrial Science, The University of Tokyo

nachricht Research reveals how order first appears in liquid crystals
23.05.2018 | Brown University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: LZH showcases laser material processing of tomorrow at the LASYS 2018

At the LASYS 2018, from June 5th to 7th, the Laser Zentrum Hannover e.V. (LZH) will be showcasing processes for the laser material processing of tomorrow in hall 4 at stand 4E75. With blown bomb shells the LZH will present first results of a research project on civil security.

At this year's LASYS, the LZH will exhibit light-based processes such as cutting, welding, ablation and structuring as well as additive manufacturing for...

Im Focus: Self-illuminating pixels for a new display generation

There are videos on the internet that can make one marvel at technology. For example, a smartphone is casually bent around the arm or a thin-film display is rolled in all directions and with almost every diameter. From the user's point of view, this looks fantastic. From a professional point of view, however, the question arises: Is that already possible?

At Display Week 2018, scientists from the Fraunhofer Institute for Applied Polymer Research IAP will be demonstrating today’s technological possibilities and...

Im Focus: Explanation for puzzling quantum oscillations has been found

So-called quantum many-body scars allow quantum systems to stay out of equilibrium much longer, explaining experiment | Study published in Nature Physics

Recently, researchers from Harvard and MIT succeeded in trapping a record 53 atoms and individually controlling their quantum state, realizing what is called a...

Im Focus: Dozens of binaries from Milky Way's globular clusters could be detectable by LISA

Next-generation gravitational wave detector in space will complement LIGO on Earth

The historic first detection of gravitational waves from colliding black holes far outside our galaxy opened a new window to understanding the universe. A...

Im Focus: Entangled atoms shine in unison

A team led by Austrian experimental physicist Rainer Blatt has succeeded in characterizing the quantum entanglement of two spatially separated atoms by observing their light emission. This fundamental demonstration could lead to the development of highly sensitive optical gradiometers for the precise measurement of the gravitational field or the earth's magnetic field.

The age of quantum technology has long been heralded. Decades of research into the quantum world have led to the development of methods that make it possible...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Save the date: Forum European Neuroscience – 07-11 July 2018 in Berlin, Germany

02.05.2018 | Event News

Invitation to the upcoming "Current Topics in Bioinformatics: Big Data in Genomics and Medicine"

13.04.2018 | Event News

Unique scope of UV LED technologies and applications presented in Berlin: ICULTA-2018

12.04.2018 | Event News

 
Latest News

Space-like gravity weakens biochemical signals in muscle formation

23.05.2018 | Life Sciences

NIST puts the optical microscope under the microscope to achieve atomic accuracy

23.05.2018 | Physics and Astronomy

Magnesium magnificent for plasmonic applications

23.05.2018 | Materials Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>