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 X-ray scattering shines light on protein folding
10.07.2020 | The Korea Advanced Institute of Science and Technology (KAIST)

nachricht Surprisingly many peculiar long introns found in brain genes
10.07.2020 | Moscow Institute of Physics and Technology

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: The spin state story: Observation of the quantum spin liquid state in novel material

New insight into the spin behavior in an exotic state of matter puts us closer to next-generation spintronic devices

Aside from the deep understanding of the natural world that quantum physics theory offers, scientists worldwide are working tirelessly to bring forth a...

Im Focus: Excitation of robust materials

Kiel physics team observed extremely fast electronic changes in real time in a special material class

In physics, they are currently the subject of intensive research; in electronics, they could enable completely new functions. So-called topological materials...

Im Focus: Electrons in the fast lane

Solar cells based on perovskite compounds could soon make electricity generation from sunlight even more efficient and cheaper. The laboratory efficiency of these perovskite solar cells already exceeds that of the well-known silicon solar cells. An international team led by Stefan Weber from the Max Planck Institute for Polymer Research (MPI-P) in Mainz has found microscopic structures in perovskite crystals that can guide the charge transport in the solar cell. Clever alignment of these "electron highways" could make perovskite solar cells even more powerful.

Solar cells convert sunlight into electricity. During this process, the electrons of the material inside the cell absorb the energy of the light....

Im Focus: The lightest electromagnetic shielding material in the world

Empa researchers have succeeded in applying aerogels to microelectronics: Aerogels based on cellulose nanofibers can effectively shield electromagnetic radiation over a wide frequency range – and they are unrivalled in terms of weight.

Electric motors and electronic devices generate electromagnetic fields that sometimes have to be shielded in order not to affect neighboring electronic...

Im Focus: Gentle wall contact – the right scenario for a fusion power plant

Quasi-continuous power exhaust developed as a wall-friendly method on ASDEX Upgrade

A promising operating mode for the plasma of a future power plant has been developed at the ASDEX Upgrade fusion device at Max Planck Institute for Plasma...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Contact Tracing Apps against COVID-19: German National Academy Leopoldina hosts international virtual panel discussion

07.07.2020 | Event News

International conference QuApps shows status quo of quantum technology

02.07.2020 | Event News

Dresden Nexus Conference 2020: Same Time, Virtual Format, Registration Opened

19.05.2020 | Event News

 
Latest News

X-ray scattering shines light on protein folding

10.07.2020 | Life Sciences

Looking at linkers helps to join the dots

10.07.2020 | Materials Sciences

Surprisingly many peculiar long introns found in brain genes

10.07.2020 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>