Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Structure of cell signaling molecule suggests general on-off switch

22.04.2013
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.

In addition to Lefkowitz and Shukla, study authors at Duke include Kunhong Xiao, Rosana I. Reis, Wei-Chou Tseng, Dean P. Staus, Li-Yin Huang and Prachi Tripathi-Shukla.

Authors from Stanford include Aashish Manglik, Andrew C. Kruse, Daniel Hilger, William I. Weis and Kobilka. Authors from the University of Chicago include Serdar Uysal, Marcin Paduch, Akiko Koide, Shohei Koide and Anthony A. Kossiakoff.

The study was funded by the Stanford Medical Scientist Training Program, the American Heart Association, the National Science Foundation, the Mathers Foundation and the National Institutes of Health (NS028471, HL16037, HL70631, GM072688, GM087519, HL 075443).

Sarah Avery | EurekAlert!
Further information:
http://www.duke.edu

More articles from Life Sciences:

nachricht How brains surrender to sleep
23.06.2017 | IMP - Forschungsinstitut für Molekulare Pathologie GmbH

nachricht A new technique isolates neuronal activity during memory consolidation
22.06.2017 | Spanish National Research Council (CSIC)

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 we see monkeys from space? Emerging technologies to map biodiversity

An international team of scientists has proposed a new multi-disciplinary approach in which an array of new technologies will allow us to map biodiversity and the risks that wildlife is facing at the scale of whole landscapes. The findings are published in Nature Ecology and Evolution. This international research is led by the Kunming Institute of Zoology from China, University of East Anglia, University of Leicester and the Leibniz Institute for Zoo and Wildlife Research.

Using a combination of satellite and ground data, the team proposes that it is now possible to map biodiversity with an accuracy that has not been previously...

Im Focus: Climate satellite: Tracking methane with robust laser technology

Heatwaves in the Arctic, longer periods of vegetation in Europe, severe floods in West Africa – starting in 2021, scientists want to explore the emissions of the greenhouse gas methane with the German-French satellite MERLIN. This is made possible by a new robust laser system of the Fraunhofer Institute for Laser Technology ILT in Aachen, which achieves unprecedented measurement accuracy.

Methane is primarily the result of the decomposition of organic matter. The gas has a 25 times greater warming potential than carbon dioxide, but is not as...

Im Focus: How protons move through a fuel cell

Hydrogen is regarded as the energy source of the future: It is produced with solar power and can be used to generate heat and electricity in fuel cells. Empa researchers have now succeeded in decoding the movement of hydrogen ions in crystals – a key step towards more efficient energy conversion in the hydrogen industry of tomorrow.

As charge carriers, electrons and ions play the leading role in electrochemical energy storage devices and converters such as batteries and fuel cells. Proton...

Im Focus: A unique data centre for cosmological simulations

Scientists from the Excellence Cluster Universe at the Ludwig-Maximilians-Universität Munich have establised "Cosmowebportal", a unique data centre for cosmological simulations located at the Leibniz Supercomputing Centre (LRZ) of the Bavarian Academy of Sciences. The complete results of a series of large hydrodynamical cosmological simulations are available, with data volumes typically exceeding several hundred terabytes. Scientists worldwide can interactively explore these complex simulations via a web interface and directly access the results.

With current telescopes, scientists can observe our Universe’s galaxies and galaxy clusters and their distribution along an invisible cosmic web. From the...

Im Focus: Scientists develop molecular thermometer for contactless measurement using infrared light

Temperature measurements possible even on the smallest scale / Molecular ruby for use in material sciences, biology, and medicine

Chemists at Johannes Gutenberg University Mainz (JGU) in cooperation with researchers of the German Federal Institute for Materials Research and Testing (BAM)...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Plants are networkers

19.06.2017 | Event News

Digital Survival Training for Executives

13.06.2017 | Event News

Global Learning Council Summit 2017

13.06.2017 | Event News

 
Latest News

Quantum thermometer or optical refrigerator?

23.06.2017 | Physics and Astronomy

A 100-year-old physics problem has been solved at EPFL

23.06.2017 | Physics and Astronomy

Equipping form with function

23.06.2017 | Information Technology

VideoLinks
B2B-VideoLinks
More VideoLinks >>>