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How living cells solved a needle in a haystack problem to produce electrical signals
Date:11/24/2013

searchers noted.

Catterall said the research team introduced just three mutations into the 274 amino acid residues of a bacterial sodium channels to create calcium channels.

"We thought if we placed the right residues in the right places, the structure should be accommodating and we could change the channel from selective for sodium to selective for calcium,' Catterall said. "Luckily it worked. We rebuilt the channel with the full physiological properties of calcium channels."

They then conducted electrophysiological and X-ray crystallography analyses to try to see what the channel looked like and how it operated. The beamline staff at the U.S. Department of Energy's Advanced Light Source, at the Lawrence Berkeley National Laboratory in California, assisted with this data collection.

The team was able to determine how the filter that selected for calcium was constructed, and to report on the pathway calcium ions likely follow as they pass through the pore.

The calcium ions, the researchers said, transition through three binding sites. The first site, in an outer vestibule near the mouth of the pore, is critical in recognizing and selectively admitting calcium ions into the channel and keeping out sodium. This role is supported by the second site inside the pore. This site is single occupancy. The calcium ion there is quickly knocked out by repulsive interactions with another calcium ion approaching from outside the cell, like pin balls ricocheting, even though it would like to bind there.

The third site, with a lower binding affinity, allows the calcium ions to move into the cell.

The flow of ions is accelerated by having these three binding sites in sequence. The flow goes only in one direction because the concentration of calcium ions outside the cell is much larger than their concentration inside the cell. At any given time, the ions also have to be in particular, mutually exclusive positions
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Contact: Leila Gray
leilag@uw.edu
206-685-0831
University of Washington
Source:Eurekalert

Page: 1 2 3

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