Navigation Links
Structure of cell signaling molecule suggests general on-off switch
Date:4/21/2013

DURHAM, N.C. A three-dimensional image of one of the proteins that serves as an on-off switch as it binds to receptors on the surface of a cell suggests there may be a sort of main power switch that could be tripped. These surface receptors are responsible for helping cells discern light, set the heart racing, or detect pain.

The finding, published online April 21, 2013, in the journal Nature by a research collaboration involving this year's Nobel laureates in chemistry, could help in the development of more effective drugs to switch on or off the cell receptors that regulate nearly every bodily function. Already, up to half of all drugs engage these receptors, including antihistamines and beta blockers, but many of the intricacies of how these important proteins work remain unknown.

"It's important to understand how this extraordinary family of receptors work," said co-author Robert J. Lefkowitz, M.D., James B. Duke Professor of Medicine and Howard Hughes Medical Institute Investigator. "This is the kind of finding that answers a basic curiosity, but can also be of benefit if we can develop new drugs or improve the ones we have."

The research marks a collaborative reunion between Lefkowitz and Brian K. Kobilka, M.D., chair of molecular and cellular physiology at Stanford University School of Medicine. The two researchers friends who first collaborated when Kobilka was a trainee in Lefkowitz's laboratory at Duke - shared the 2012 Nobel Prize in Chemistry for their discoveries involving the G-protein coupled receptors (GPCRs), which are activated by signaling proteins to detect hormones, neurotransmitters, pain, light.

In the current work, the researchers used X-ray crystallography to develop an atom-scale image of one of the principal signaling molecules that regulate GPCRs. This protein is called beta-arrestin1, which, among other things, works to dim a cell's response to hormones such as adrenalin.

The researchers were able to isolate and capture the beta-arrestin1 protein in an active state as it binds to a segment of the GPCR a first. That snapshot, in high resolution, revealed that the structural conformation or shape of the protein in its active state is strikingly different than when it is inactive.

Such changes suggest there may be a general molecular mechanism that activates the beta-arrestin1 a sort of main switch that controls the multi-functional signaling proteins.

"It's like there are brakes on in beta-arrestin1, and then when the beta-arrestin1 binds to a GPCR, the brakes are released, thereby activating beta-arrestin1," said Arun K. Shukla, PhD, assistant professor of medicine at Duke and co-lead author of the study.

The researchers are now pursuing additional structural imaging of the signaling complex consisting of beta-arrestin1 and the entire receptor protein.


'/>"/>

Contact: Sarah Avery
sarah.avery@duke.edu
919-660-1306
Duke University Medical Center
Source:Eurekalert

Related biology news :

1. Study led by NUS researchers proves the existence of 3 overstretched DNA structures
2. Mainz scientists confirm original tetrahedral model of the molecular structure of water
3. A*STAR scientists groundbreaking discovery of nucleus structure crucial to understanding diseases
4. Newly discovered plant structure may lead to improved biofuel processing
5. Nanostructures with living cells
6. Protein structure: Immune system foiled by a hairpin
7. Novel technique reveals dynamics of telomere DNA structure
8. Scientists discover structure of protein essential for quality control, nerve function
9. Banded mongooses structure monosyllabic sounds in a similar way to humans
10. New study defines the long-sought structure of a protein necessary for cell-cell interaction
11. Nanoengineers can print 3D microstructures in mere seconds
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:2/2/2016)... 2, 2016  BioMEMS devices deployed in ... on medical screening and diagnostic applications, such ... devices that facilitate and assure continuous monitoring ... are being bolstered through new opportunities offered ... acquisition coupled with wireless connectivity and low ...
(Date:2/2/2016)... Va. , Feb. 2, 2016   ... award from the U.S. Army Research Office and ... the range and sensitivity of the company,s ... Past Accounting Mission and, more generally, defense-related DNA ... DNA phenotyping capabilities (predicting appearance and ancestry from ...
(Date:2/1/2016)... 2016  Wocket® smart wallet ( www.wocketwallet.com ) announces the launch of ... Fatone . Las Vegas , where Joey appeared ... Las Vegas , where Joey appeared at the Wocket ... video ad was filmed at the Consumer Electronics Show (CES2016) in ... to meet and greet fans. --> ...
Breaking Biology News(10 mins):
(Date:2/8/2016)... Inc. today announced that Director Robert A. Ingram has ... addition, Robert Keegan has been appointed to the Board ... --> North Carolina . --> ... $32.8 million of net proceeds in a private Mezzanine B financing ... Research Triangle area of North Carolina . ...
(Date:2/8/2016)... ... February 08, 2016 , ... Franz ... Semantic Graph Database technology, today announced the availability of AllegroGraph 6, the leading ... the Cloudera Certified Technology Program (CCPT). AllegroGraph is the first Semantic ...
(Date:2/6/2016)... (PRWEB) , ... February 06, 2016 , ... The Center ... cost-free, for middle and high school teachers on Wednesday February 10, 2016. This ... at the Smithsonian-Mason School of Conservation, located at 1500 Remount Road in Front Royal, ...
(Date:2/5/2016)... , February 5, 2016 ... a biotechnology company focused on developing products for Regenerative ... requested Rare Pediatric Disease Designation (RPDD) from the US ... (RP) with MANF. MANF was previously granted orphan drug ... --> Amarantus BioScience Holdings, Inc. ...
Breaking Biology Technology: