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Small change makes a big difference for ion channels
Date:6/2/2011

CHAMPAIGN, Ill. 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 protein
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Contact: Liz Ahlberg
eahlberg@illinois.edu
217-244-1073
University of Illinois at Urbana-Champaign
Source:Eurekalert  

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