Featured Research

from universities, journals, and other organizations

Free-energy Theory Borne Out In Large-scale Protein Folding

Date:
October 4, 2005
Source:
Rice University
Summary:
Scientists at Rice University have combined theory and experiment for the first time to both predict theoretically and verify experimentally the protein-folding dynamics of a large, complex protein. The interdisciplinary research appears this week in two back-to-back papers in the Proceedings of the National Academy of Sciences. The study involved pioneering efforts to establish comparable experimental and theoretical data, and Rice's team believes the method can be applied to other proteins.

Studies at Rice University were carried out on a protein known as MLAc, a variant of the protein used by the bacterium E. coli to regulate its system for metabolizing lactose, the sugar found in milk. This image gives an artist's impression of MLAc in the process of folding. Like all proteins, MLAc consists of a chain of smaller building-block molecules known as amino acids--about 360 of them in this case. They are depicted here like beads on a string. This chain, in turn, twists and turns to create larger subunits known as "domains," which are depicted here in different colors.
Credit: Corey J. Wilson, Cecilia Clementi, Payel Das, Pernilla Wittung-Stafshede, and Kathleen Matthews

HOUSTON, Oct. 3, 2005 -- In unprecedented new research, scientists atRice University have combined theory and experiment for the first timeto both predict theoretically and verify experimentally theprotein-folding dynamics of a large, complex protein.

The interdisciplinary research appears this week in two back-to-backpapers in the Proceedings of the National Academy of Sciences.

"Researchers have successfully combined computer modeling andexperimental results in folding studies for small proteins, but this isthe first effective combination for a large, multi-domain protein,"said study co-author Kathleen Matthews, Dean of the Wiess School ofNatural Sciences and Stewart Memorial Professor of Biochemistry."Pioneering efforts were required to establish comparable experimentaland theoretical data, and the method worked remarkably well. We expectothers to adopt it in their own studies."

Proteins are the workhorses of biology. At any given time, eachcell in our bodies contains 10,000 or more of them. Each of theseproteins is a chain of amino acids strung end-to-end like beads innecklace. For longer proteins, the chain can contain hundreds of aminoacids.

Thanks to modern genomics, scientists can use DNA to decipherthe amino acid sequence in a protein. But knowing the sequence gives noclue to the protein's function, because function is inextricably tiedto shape, and every protein self-assembles into its characteristicshape within seconds of being created.

"The folded, functional form of the protein is what reallymatters, and our interest is in creating a folding roadmap of sorts, aplot of the thermodynamic route that the protein follows as it movestoward equilibrium," said co-author Cecilia Clementi, the NormanHackerman-Welch Young Investigator Assistant Professor of Chemistry.

The Rice research team included Clementi, Clementi's graduatestudent Payel Das, experimentalist Pernilla Wittung-Stafshede,associate professor of biochemistry and cell biology, Matthews andgraduate student Corey Wilson of biochemistry and cell biology.

"We know that misfolded proteins play a key but mysterious rolein Alzheimer's, Parkinson's, diabetes and a host of other diseases, somapping the normal route a protein takes � and finding the off-rampsthat might lead to misfolding � are vitally important,"Wittung-Stafshede said.

Rice's studies were carried out on monomeric lactose repressorprotein, or MLAc, a variant of the protein used by E. coli to regulateexpression of the proteins that transport and metabolize lactose. MLAccontains about 360 amino acids.

While scientists know proteins containing 100 or fewer aminoacids fold in a very cooperative (all-or-none) fashion, it is believedthat larger proteins fold through the formation of partially foldedintermediate structures before settling into their final state.

Simulating large-scale protein folding is too complex for eventhe most powerful supercomputer. In developing a theoretical approachthat allows studying protein folding on a computer, Clementi and Dasrelied on the techniques of statistical mechanics, building up anoverall picture of MLAc folding based upon statistical approximationsof molecular events.

On the experimental side, Wittung-Stafshede, Matthews andWilson prepared samples of MLAc and added urea to cause them to unfold.The team then injected water into the solution very fast, diluting themixture and causing the proteins to fold. Using spectroscopy, theycaptured fluorescence and ultraviolet polarization patterns given offby the proteins as they folded.

"The novelty of this work is the direct and quantitativecomparison of the time-dependent simulation data with the experimentalmeasurements from circular dichroism and tryptophan fluorescence," Dassaid. "The excellent agreement between experiment and theoryillustrates that the existence of a well-defined "folding route", atleast for large proteins, can be predicted within the framework offree-energy landscape theory. This has been a very controversial issuein the field of protein folding."

Study co-authors also included Giovanni Fossati, assistantprofessor of physics and astronomy, who helped the team analyze andinterpret the simulation data.

###

The research was funded bythe National Science Foundation, the National Institutes of Health, theTexas Advanced Technology Program and the Welch Foundation.


Story Source:

The above story is based on materials provided by Rice University. Note: Materials may be edited for content and length.


Cite This Page:

Rice University. "Free-energy Theory Borne Out In Large-scale Protein Folding." ScienceDaily. ScienceDaily, 4 October 2005. <www.sciencedaily.com/releases/2005/10/051004085114.htm>.
Rice University. (2005, October 4). Free-energy Theory Borne Out In Large-scale Protein Folding. ScienceDaily. Retrieved July 23, 2014 from www.sciencedaily.com/releases/2005/10/051004085114.htm
Rice University. "Free-energy Theory Borne Out In Large-scale Protein Folding." ScienceDaily. www.sciencedaily.com/releases/2005/10/051004085114.htm (accessed July 23, 2014).

Share This




More Matter & Energy News

Wednesday, July 23, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Robot Parking Valet Creates Stress-Free Travel

Robot Parking Valet Creates Stress-Free Travel

AP (July 23, 2014) 'Ray' the robotic parking valet at Dusseldorf Airport in Germany lets travelers to avoid the hassle of finding a parking spot before heading to the check-in desk. (July 23) Video provided by AP
Powered by NewsLook.com
Boeing Ups Outlook on 52% Profit Jump

Boeing Ups Outlook on 52% Profit Jump

Reuters - Business Video Online (July 23, 2014) Commercial aircraft deliveries rose seven percent at Boeing, prompting the aerospace company to boost full-year profit guidance- though quarterly revenues missed analyst estimates. Bobbi Rebell reports. Video provided by Reuters
Powered by NewsLook.com
Europe's Car Market on the Rebound?

Europe's Car Market on the Rebound?

Reuters - Business Video Online (July 23, 2014) Daimler kicks off a round of second-quarter earnings results from Europe's top carmakers with a healthy set of numbers - prompting hopes that stronger sales in Europe will counter weakness in emerging markets. Hayley Platt reports. Video provided by Reuters
Powered by NewsLook.com
9/11 Commission Members Warn of Terror "fatigue" Among American Public

9/11 Commission Members Warn of Terror "fatigue" Among American Public

Reuters - US Online Video (July 22, 2014) Ten years after releasing its initial report, members of the 9/11 Commission warn of the "waning sense of urgency" in combating terrorists attacks. Mana Rabiee reports. Video provided by Reuters
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins