Featured Research

from universities, journals, and other organizations

3-D structure of an unmodified G protein-coupled receptor in its natural habitat

Date:
October 22, 2012
Source:
University of California - San Diego
Summary:
Scientists have determined the three-dimensional structure of a complete, unmodified G-protein-coupled receptor in its native environment: embedded in a membrane in physiological conditions.

Scientists have determined the three-dimensional structure of a complete, unmodified G-protein-coupled receptor in its native environment: embedded in a membrane in physiological conditions.

Using NMR spectroscopy, the team mapped the arrangement of atoms in a protein called CXCR1, which detects the inflammatory signal interleukin 8 and, through a G protein located inside the cell, triggers a cascade of events that can mobilize immune cells, for example.

Because G protein-coupled receptors are critical for many cellular responses to external signals, they have been a major target for drugs. More precise knowledge of the shapes of these receptors will allow drugmakers to tailor small molecules to better fit specific targets, avoiding collateral hits that can cause detrimental side effects.

"This finding will have a major impact on structure-based drug development since for the first time the principal class of drug receptors can be studied in their biologically active forms where they interact with other proteins and potential drugs," said Stanley Opella, professor of chemistry and biochemistry at the University of California, San Diego who led the work, which Nature published online October 21st in advance of the print edition.

Protein structures are most often determined by reading the diffraction patterns of X-rays beamed at their crystalline form, but crystallizing such large, unwieldy molecules is a challenge often met with strategies such as snipping off floppy ends.

Those changes can alter the shape of critical regions of the protein. "Our approach was to not touch the protein," Opella said. "We are working with molecules in their active form."

Their strategy has revealed a new view of these receptors. Previous reports have all noted seven helices weaving through the membrane. Opella's group sees an eighth lying on the membrane surface, a trait that at least some other G protein-coupled receptors must share.

And the loops inside and outside of the cell are structured. "For years people thought the loops were mobile. They're not," Opella said. "The signals we get from the loops aren't any weaker than the other parts of the protein as they would be if they were waving about."

CXCR1 has been implicated in the progression of several types of cancer. In one example, preclinical studies have shown that blocking this receptor inhibits the undifferentiated stem cells within breast cancer tumors, leading to the death of all tumor cell types and stopping them from seeding new tumors.

Opella and colleagues hope this finding along with continuing studies of changes in this receptor's configuration as it binds to interleukin 8 and drug candidate will lead to more effective and less harmful cancer treatments.


Story Source:

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


Journal Reference:

  1. Sang Ho Park, Bibhuti B. Das, Fabio Casagrande, Ye Tian, Henry J. Nothnagel, Mignon Chu, Hans Kiefer, Klaus Maier, Anna A. De Angelis, Francesca M. Marassi, Stanley J. Opella. Structure of the chemokine receptor CXCR1 in phospholipid bilayers. Nature, 2012; DOI: 10.1038/nature11580

Cite This Page:

University of California - San Diego. "3-D structure of an unmodified G protein-coupled receptor in its natural habitat." ScienceDaily. ScienceDaily, 22 October 2012. <www.sciencedaily.com/releases/2012/10/121022113602.htm>.
University of California - San Diego. (2012, October 22). 3-D structure of an unmodified G protein-coupled receptor in its natural habitat. ScienceDaily. Retrieved July 23, 2014 from www.sciencedaily.com/releases/2012/10/121022113602.htm
University of California - San Diego. "3-D structure of an unmodified G protein-coupled receptor in its natural habitat." ScienceDaily. www.sciencedaily.com/releases/2012/10/121022113602.htm (accessed July 23, 2014).

Share This




More Plants & Animals News

Wednesday, July 23, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Stone Fruit Listeria Scare Causes Sweeping Recall

Stone Fruit Listeria Scare Causes Sweeping Recall

Newsy (July 22, 2014) The Wawona Packing Company has issued a voluntary recall on the stone fruit it distributes due to a possible Listeria outbreak. Video provided by Newsy
Powered by NewsLook.com
Michigan Plant's Goal: Flower and Die

Michigan Plant's Goal: Flower and Die

AP (July 22, 2014) An 80-year-old agave plant, which is blooming for the first and only time at a University of Michigan conservatory, will die when it's done (July 22) Video provided by AP
Powered by NewsLook.com
Huge Schizophrenia Study Finds Dozens Of New Genetic Causes

Huge Schizophrenia Study Finds Dozens Of New Genetic Causes

Newsy (July 22, 2014) The 83 new genetic markers could open dozens of new avenues for schizophrenia treatment research. Video provided by Newsy
Powered by NewsLook.com
CDC Head Concerned About a Post-Antibiotic Era

CDC Head Concerned About a Post-Antibiotic Era

AP (July 22, 2014) Sounding alarms about the growing threat of antibiotic resistance, CDC Director Tom Frieden warned Tuesday if the global community does not confront the problem soon, the world will be living in a devastating post-antibiotic era. (July 22) Video provided by AP
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