Featured Research

from universities, journals, and other organizations

Physicists help biologists to understand protein folding

Date:
June 20, 2010
Source:
University of California - Santa Barbara
Summary:
Physicists have created a microscopic device to assist biologists in making very fast molecular measurements that aid the understanding of protein folding. This development may help elucidate biological processes associated with diseases such as Alzheimer's and Parkinson's. Since proteins in the body perform different functions according to their shape, the folding process is considered a key area of study.

Physicists at UC Santa Barbara have created a microscopic device to assist biologists in making very fast molecular measurements that aid the understanding of protein folding. This development may help elucidate biological processes associated with diseases such as Alzheimer's and Parkinson's. Since proteins in the body perform different functions according to their shape, the folding process is considered a key area of study.

Using a microfabricated fluid mixing device built at UCSB's nanofabrication facility, UCSB physicists and their collaborators from the University of Zurich have made the first sub-second, single-molecule measurements of an essential biological molecule known as a chaperonin. The results are published in the Proceedings of the National Academy of Sciences.

"The genes encoded in DNA contain chemical sequences for proteins, which, once they have been synthesized in the cell, fold into molecular machines that perform the basic functions of living things," said Everett Lipman, co-author and assistant professor of physics at UCSB. "Many proteins can fold on their own, but others are prone to misfolding and aggregation, which are thought to cause neurodegenerative diseases such as Alzheimer's and Parkinson's."

Chaperonins are known to assist the folding of other proteins, called substrates, and to prevent aggregation, Lipman explained. GroEL, a member of a large family of chaperonins, works in concert with GroES to encapsulate a substrate protein, isolating it as it folds. Although this process has been studied previously, the mechanism by which the chaperonin functions or fails to function is not yet understood.

Single-molecule experiments provide information about protein folding that would otherwise be obscured by averaging signals from the many billions of unsynchronized molecules in a typical ensemble experiment. Until now, the slow speed of manual mixing prevented single-molecule measurements of folding inside chaperonins at times earlier than a few minutes. This is far slower than the fifth of a second needed for GroEL and GroES to encapsulate their substrate.

UCSB physics graduate student Shawn Pfeil, working with Lipman and fellow student Charlie Wickersham, designed and built a device that enables single-molecule measurements as fast as five milliseconds. Fluids were mixed in a channel one-tenth the size of a human hair. With collaborators Armin Hoffmann and Benjamin Schuler at the Biochemical Institute of the University of Zurich, they measured the folding of rhodanese, an enzyme responsible for detoxification of cyanide, inside the GroEL-GroES chaperone complex.

The results show that -- contrary to what was previously believed -- the fast initial capping of the chaperonin cavity by GroES and the related conformational change of GroEL do not initiate folding of the substrate, explained Lipman. Extensive measurements on time scales from milliseconds to hours indicate that the chaperonin slows the folding of one portion of the rhodanese protein, allowing it to find the correct folded shape while it is protected from aggregation. Further studies using this new method may help to determine whether the failure of chaperonins is responsible for pathogenic aggregation, clumping of protein, that leads to disease.

Lipman has collaborated with Schuler for over a decade. They met while working as postdoctoral fellows at the National Institutes of Health. The new device builds on an earlier device they developed in 2003. "The microfluidic device we used for the 2003 experiment was slow, and it generated a lot of background noise," he said. "By designing a mixer specifically for single-molecule measurements, we were able to obtain the greatly improved time resolution and sensitivity necessary to measure folding inside a chaperonin."


Story Source:

The above story is based on materials provided by University of California - Santa Barbara. Note: Materials may be edited for content and length.


Journal Reference:

  1. H. Hofmann, F. Hillger, S. H. Pfeil, A. Hoffmann, D. Streich, D. Haenni, D. Nettels, E. A. Lipman, B. Schuler. Single-molecule spectroscopy of protein folding in a chaperonin cage. Proceedings of the National Academy of Sciences, 2010; DOI: 10.1073/pnas.1002356107

Cite This Page:

University of California - Santa Barbara. "Physicists help biologists to understand protein folding." ScienceDaily. ScienceDaily, 20 June 2010. <www.sciencedaily.com/releases/2010/06/100617132222.htm>.
University of California - Santa Barbara. (2010, June 20). Physicists help biologists to understand protein folding. ScienceDaily. Retrieved July 24, 2014 from www.sciencedaily.com/releases/2010/06/100617132222.htm
University of California - Santa Barbara. "Physicists help biologists to understand protein folding." ScienceDaily. www.sciencedaily.com/releases/2010/06/100617132222.htm (accessed July 24, 2014).

Share This




More Matter & Energy News

Thursday, July 24, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Creative Makeovers for Ugly Cellphone Towers

Creative Makeovers for Ugly Cellphone Towers

AP (July 24, 2014) Mobile phone companies and communities across the country are going to new lengths to disguise those unsightly cellphone towers. From a church bell tower to a flagpole, even a pencil, some towers are trying to make a point. (July 24) Video provided by AP
Powered by NewsLook.com
Algonquin Power Goes Activist on Its Target Gas Natural

Algonquin Power Goes Activist on Its Target Gas Natural

TheStreet (July 23, 2014) When The Deal's Amanda Levin exclusively reported that Gas Natural had been talking to potential suitors, the Ohio company responded with a flat denial, claiming its board had not talked to anyone about a possible sale. Lo and behold, Canadian utility Algonquin Power and Utilities not only had approached the company, but it did it three times. Its last offer was for $13 per share as Gas Natural's was trading at a 60-day moving average of about $12.50 per share. Now Algonquin, which has a 4.9% stake in Gas Natural, has taken its case to shareholders, calling on them to back its proposals or, possibly, a change in the target's board. Video provided by TheStreet
Powered by NewsLook.com
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

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