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 Water forms 'spine of hydration' around DNA, group finds
26.05.2017 | Cornell University

nachricht How herpesviruses win the footrace against the immune system
26.05.2017 | Helmholtz-Zentrum für Infektionsforschung

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 the immune system be boosted against Staphylococcus aureus by delivery of messenger RNA?

Staphylococcus aureus is a feared pathogen (MRSA, multi-resistant S. aureus) due to frequent resistances against many antibiotics, especially in hospital infections. Researchers at the Paul-Ehrlich-Institut have identified immunological processes that prevent a successful immune response directed against the pathogenic agent. The delivery of bacterial proteins with RNA adjuvant or messenger RNA (mRNA) into immune cells allows the re-direction of the immune response towards an active defense against S. aureus. This could be of significant importance for the development of an effective vaccine. PLOS Pathogens has published these research results online on 25 May 2017.

Staphylococcus aureus (S. aureus) is a bacterium that colonizes by far more than half of the skin and the mucosa of adults, usually without causing infections....

Im Focus: A quantum walk of photons

Physicists from the University of Würzburg are capable of generating identical looking single light particles at the push of a button. Two new studies now demonstrate the potential this method holds.

The quantum computer has fuelled the imagination of scientists for decades: It is based on fundamentally different phenomena than a conventional computer....

Im Focus: Turmoil in sluggish electrons’ existence

An international team of physicists has monitored the scattering behaviour of electrons in a non-conducting material in real-time. Their insights could be beneficial for radiotherapy.

We can refer to electrons in non-conducting materials as ‘sluggish’. Typically, they remain fixed in a location, deep inside an atomic composite. It is hence...

Im Focus: Wafer-thin Magnetic Materials Developed for Future Quantum Technologies

Two-dimensional magnetic structures are regarded as a promising material for new types of data storage, since the magnetic properties of individual molecular building blocks can be investigated and modified. For the first time, researchers have now produced a wafer-thin ferrimagnet, in which molecules with different magnetic centers arrange themselves on a gold surface to form a checkerboard pattern. Scientists at the Swiss Nanoscience Institute at the University of Basel and the Paul Scherrer Institute published their findings in the journal Nature Communications.

Ferrimagnets are composed of two centers which are magnetized at different strengths and point in opposing directions. Two-dimensional, quasi-flat ferrimagnets...

Im Focus: World's thinnest hologram paves path to new 3-D world

Nano-hologram paves way for integration of 3-D holography into everyday electronics

An Australian-Chinese research team has created the world's thinnest hologram, paving the way towards the integration of 3D holography into everyday...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Marine Conservation: IASS Contributes to UN Ocean Conference in New York on 5-9 June

24.05.2017 | Event News

AWK Aachen Machine Tool Colloquium 2017: Internet of Production for Agile Enterprises

23.05.2017 | Event News

Dortmund MST Conference presents Individualized Healthcare Solutions with micro and nanotechnology

22.05.2017 | Event News

 
Latest News

How herpesviruses win the footrace against the immune system

26.05.2017 | Life Sciences

Water forms 'spine of hydration' around DNA, group finds

26.05.2017 | Life Sciences

First Juno science results supported by University of Leicester's Jupiter 'forecast'

26.05.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>