. Earth Science News .

Small change makes a big difference for ion channels
by Liz Ahlberg
Physical Sciences Editor
Champaign, IL (SPX) Jun 07, 2011

Illinois professor Claudio Grosman and research scientist Gisela Cymes used a high-resolution single-molecule study technique to see the very subtle differences between two branches of an important family of neurotransmitter-gated ion channels. Photo courtesy L. Brian Stauffer.

Using a high-resolution single-molecule study technique, University of Illinois researchers have seen the very subtle differences between two branches of an important family of neurotransmitter-gated ion channels.

Professor Claudio Grosman and research scientist Gisela Cymes published their work in the journal Nature.

Nicotinic-type receptors are proteins embedded in the membranes of nerve and muscle cells that regulate activity. A neurotransmitter, such as acetylcholine, triggers a small conformation change in the protein that opens a channel and allows ions to flow into the cell. These receptors are key players in muscle motion and neurological diseases such as epilepsy.

The protein family is divided into two classes, with very similar structure but different function: One mediates inhibition by channeling anions, or negatively charged ions, while the other mediates excitation by channeling positively charged cations.

"This is the yin and yang of the central nervous system," said Grosman, a professor of molecular and integrative physiology, of biophysics and of neuroscience.

"The anion members of the family and the cation members of the family pretty much look the same. The overall structure is the same. So, the question is, what is the reason for the different charge selectivity?"

The team focused on the segment of protein lining the inside of the channel. The two types of channels display very small differences in their sequence of amino acids, the building blocks of proteins. Both the anion-selective and cation-selective channels have a ring of basic amino acids, lysine or arginine, which generally carry a positive charge.

This makes sense for an anion-selective channel, but raises some questions about why cations are not repelled by these positive charges.

The charge of amino acid residues is a fundamental aspect of protein function and structure. In order to model proteins computationally, researchers have to assign a charge to each residue, so they rely on the charge the amino acid would display in bulk water - for example, assuming that basic residues are always positively charged.

However, proteins offer a much more complex environment, and it can be difficult for researchers to determine whether a particular amino acid has accepted or lost a proton to become charged.

Grosman and Cymes use an approach called patch-clamp recording, a single-molecule technique that allows them to measure binding and unbinding of single protons in functioning molecules, something that other powerful approaches cannot achieve.

With patch-clamp recording, the researchers could see the charge state of working ion channels in living cells. They saw that, in anion-selective channels, the basic residues appear to have the expected positive charge.

However, in the cation-selective channels, the lysine or arginine seems to be tucked into the protein structure so that it cannot accept a proton from the surrounding environment and instead remains neutral. This allows cation-selective channels to keep the basic residues in their sequential place without having to substitute them with other amino acids.

"These channels are the subject of a lot of computational studies. Before this paper, if researchers had to model these channels, they would always run the simulation with all the ionizable residues charged, and the simulation could well be wrong," Grosman said.

"With small tweaks, changing the position of the amino acid changes its properties. For a lysine to be protonated or deprotonated is a big difference. It's not trivial."

"Overall, we want to emphasize the notion that the properties of these chargeable amino acids depends strongly on their particular microenvironment in the whole protein," Grosman added.

While the study focused on muscle acetylcholine receptors, Grosman believes the "tucked-in" principle holds true for the entire superfamily of nicotinic-type receptors.

Next, they plan to use the patch-clamp technique to further investigate the amino acids neighboring the lysine or arginine to gain a greater understanding of how this class of proteins regulates inhibition and excitation.

"This approach has opened a window and we can start understanding things that were intractable until now," said Grosman. "This is important because it brings us closer to what the protein actually looks like if we want to understand how it works."

Related Links
University of Illinois
All About Human Beings and How We Got To Be Here

Get Our Free Newsletters Via Email
Buy Advertising Editorial Enquiries

. Comment on this article via your Facebook, Yahoo, AOL, Hotmail login.

Share this article via these popular social media networks
del.icio.usdel.icio.us DiggDigg RedditReddit GoogleGoogle

Early hominin landscape use
Leipzig, Germany (SPX) Jun 07, 2011
So far, ranging and residence patterns amongst early hominins have been indirectly inferred from morphology, stone tool sourcing, comparison to living primates and phylogenetic models. An international team of researchers including Sandi Copeland, Vaughan Grimes and Michael Richards of the Max Planck Institute for Evolutionary Anthropology in Leipzig/Germany have now investigated landscape ... read more

Japan doubles plant radiation leak estimate

Japan to report nuclear 'melt-throughs' to UN

Oxfam probes Pakistan flood 'irregularities'

Australians develop 'smart' bandage

Phase Change Memory-Based Moneta System Points to the Future of Computer Storage

Thomas Edison also invented the concrete house

3-D model mimics volcanic explosions

This is what the margins of the Ebro looked like 6 million years ago

Algal turf scrubbers clean water with sunlight

From seawater to freshwater with a nanotechnology filter

Freshwater algae mystery solved

Jellyfish blooms shunt food energy from fish to bacteria

New map reveals giant fjords beneath East Antarctic ice sheet

Support for local community programs key to climate change response in Arctic

Arctic access set to diminish by land but improve by sea

Assessing the influence of Alaska glaciers is slippery work

Viruses are 'new normal' for honey bees: study

Dubai looks to bag top spot as tea goes green

Ancient farmers chose rice attributes

Belarus ready to sell top potash firm: report

Chile volcano ash disrupts regional air travel

Floods kill 13 as heavy rains pound Haiti

Atlantic hurricane season sticks to the calendar: System 93L

Six dead in torrential Haiti rains: official

Burkina Faso arrests 93 soldiers after mutiny: officer

Six soldiers, girl killed as Burkina mutiny quelled

Fresh looting in Burkina's second-largest city

Obama has 'deep concern' over Sudan forces in Abyei

Small change makes a big difference for ion channels

Early hominin landscape use

World-Wide Assessment Determines Differences in Cultures

Historic mound in Britain 4,000 years old

Memory Foam Mattress Review
Newsletters :: SpaceDaily Express :: SpaceWar Express :: TerraDaily Express :: Energy Daily
XML Feeds :: Space News :: Earth News :: War News :: Solar Energy News

The content herein, unless otherwise known to be public domain, are Copyright 1995-2011 - Space Media Network. AFP and UPI Wire Stories are copyright Agence France-Presse and United Press International. ESA Portal Reports are copyright European Space Agency. All NASA sourced material is public domain. Additional copyrights may apply in whole or part to other bona fide parties. Advertising does not imply endorsement,agreement or approval of any opinions, statements or information provided by Space Media Network on any Web page published or hosted by Space Media Network. Privacy Statement