Researchers 'see' structure of open nicotinic acetylcholine io...(nt through a single ion channel an innov...)

Date:4/7/2008

nt through a single ion channel, an innovation that won them a Nobel Prize in 1991. Claudio Grosman, a professor of molecular and integrative physiology at Illinois, and Gisela D. Cymes, a postdoctoral associate in his lab, adopted this technique, and predicted that they could use it as a tool for what they call in vivo, time-resolved structural biology.

In a study published in 2005, the Grosman lab showed that ionizable amino acids (that is, those that may alternately be charged or neutral) can be engineered into the inner lining of the channel pore. These changes to the amino acid sequence alter the current, revealing the structure of the open-channel conformation in unprecedented detail.

As the ionizable amino acids bind and release protons from the watery environment, the pore gains or loses a positive charge that interferes with the normal flow of cations through the channel, Grosman said.

After analyzing the data, Grosmans team demonstrated that the discrete changes in current reflect the position of each mutated amino acid in the channel and the extent to which water molecules penetrate the membrane protein.

This approach allowed Grosmans team to map the relative position of every amino acid that formed the ion channel.

The new study extends this work to more distant portions of the protein.

After comparing these findings to direct studies of the structure of the closed channel, Grosman concluded that the conformational changes that allow the channel to open are quite subtle. The five subunits that make up the protein channel do not rotate or pivot dramatically when opening the gate.

There are many good reasons why I think a subtle conformational change is advantageous from an evolutionary point of view, Grosman said.

Muscle nicotinic receptors must respond to acetylcholine with staggering speed, opening within microseconds of their exposure to the neurotransmitter.

These ion cha
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Contact: Diana Yates diya@uiuc.edu 217-333-5802 University of Illinois at Urbana-Champaign Source:Eurekalert

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