Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Thanks to rare alpine bacteria, researchers identify one of alcohol's key gateways to the brain

26.04.2013
Thanks to a rare bacteria that grows only on rocks in the Swiss Alps, researchers at The University of Texas at Austin and the Pasteur Institute in France have been the first to identify how alcohol might affect key brain proteins.

It's a major step on the road to eventually developing drugs that could disrupt the interaction between alcohol and the brain.


This shows: (a) Stereo view of protein atoms neighbouring one ethanol molecule (orange) in the co-crystal structure with GLIC F14ŒA. Dotted lines indicate putative hydrogen bonds with the backbone carbonyl of N200 in the left-hand subunit (dark grey) and with N15Œ and E19Œ in the right-hand subunit (light grey). (b) Protein atoms neighboring one molecule of 2-bromoethanol (orange) in the co-crystal structure with GLIC F14ŒA, displayed as in a. Sigma-A-averaged electron density surrounding ethanol and 2-bromoethanol are contoured at 1.0 ƒÐ (blue mesh) and bromine-anomalous map is contoured at 5.0 ƒÐ (magenta mesh).

Credit: Nature Communications

"Now that we've identified this key brain protein and understand its structure, it's possible to imagine developing a drug that could block the binding site," said Adron Harris, professor of biology and director of the Waggoner Center for Alcohol and Addiction at The University of Texas at Austin.

Harris and his former postdoctoral fellow Rebecca Howard, now an assistant professor at Skidmore College, are co-authors on the paper that was recently published in Nature Communications. It describes the structure of the brain protein, called a ligand-gated ion channel, that is a key enabler of many of the primary physiological and behavioral effects of alcohol.

Harris said that for some time there has been suggestive evidence that these ion channels are important binding sites for alcohol. Researchers couldn't prove it, however, because they couldn't crystallize the brain protein well enough, and therefore couldn't use X-ray crystallography to determine the structure of the protein with and without alcohol present.

"For many of us in the alcohol field, this has been a Holy Grail, actually finding a binding site for alcohol on the brain proteins and showing it with X-ray crystallography," said Harris. "But it hasn't been possible because it is not possible to get a nice crystal."

The breakthrough came when Marc Delarue and his colleagues at the Pasteur Institute sequenced the genome of cyanobacteria Gloeobacter violaceus. They noted a protein sequence on the bacteria that is remarkably similar to the sequence of a group of ligand-gated ion channels in the human brain. They were able to crystallize this protein. Harris saw the results and immediately got in touch.

"This is something you never would have found with any sort of logical approach," he said. "You never would have guessed that this obscure bacterium would have something that looks like a brain protein in it. But the institute, because of Pasteur's fascination with bacteria, has this huge collection of obscure bacteria, and over the last few years they've been sequencing the genomes, keeping an eye out for interesting properties."

Harris and Howard asked their French colleagues to collaborate, got the cyanobacteria, changed one amino acid to make it sensitive to alcohol, and then crystallized both the original bacteria and the mutated one. They compared the two to see whether they could identify where the alcohol bound to the mutant. With further tests they confirmed that it was a meaningful site.

"Everything validated that the cavity in which the alcohol bound is important," said Harris. "It doesn't account for all the things that alcohol does, but it appears to be important for a lot of them, including some of the 'rewarding' effects and some of the negative, aversive effects."

Going forward, Harris and his lab plan to use mice to observe how changes to the key protein affect behavior when the mice consume alcohol.

They're also hoping to identify other important proteins from this family of ligand-gated ion channels. In the long term, he hopes to be involved in developing drugs that act on these proteins in ways that help people diminish or cease their drinking.

"So why do some people drink moderately and some excessively?" he said. "One reason lies in that the balance between the rewarding and the aversive effects, and that balance is different for different people, and it can change within an individual depending on their drinking patterns. Some of those effects are determined by the interactions of alcohol and these channels, so the hope is that we can alter the balance. Maybe we can diminish the reward or increase the aversive effects."

Adron Harris | EurekAlert!
Further information:
http://www.utexas.edu

Further reports about: X-ray crystallography X-ray microscopy brain protein

More articles from Life Sciences:

nachricht Modern genetic sequencing tools give clearer picture of how corals are related
17.08.2017 | University of Washington

nachricht The irresistible fragrance of dying vinegar flies
16.08.2017 | Max-Planck-Institut für chemische Ökologie

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Fizzy soda water could be key to clean manufacture of flat wonder material: Graphene

Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.

As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...

Im Focus: Exotic quantum states made from light: Physicists create optical “wells” for a super-photon

Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.

Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...

Im Focus: Circular RNA linked to brain function

For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.

While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...

Im Focus: RAVAN CubeSat measures Earth's outgoing energy

An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.

The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...

Im Focus: Scientists shine new light on the “other high temperature superconductor”

A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.

Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Call for Papers – ICNFT 2018, 5th International Conference on New Forming Technology

16.08.2017 | Event News

Sustainability is the business model of tomorrow

04.08.2017 | Event News

Clash of Realities 2017: Registration now open. International Conference at TH Köln

26.07.2017 | Event News

 
Latest News

Gold shines through properties of nano biosensors

17.08.2017 | Physics and Astronomy

Greenland ice flow likely to speed up: New data assert glaciers move over sediment, which gets more slippery as it gets wetter

17.08.2017 | Earth Sciences

Mars 2020 mission to use smart methods to seek signs of past life

17.08.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>