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At age 30, Dutch biologist Freek Vonk has built up a respectable career as a snake scientist. But in his home country,...
Since arriving on the island of Guam in the 1940s, the brown tree snake ( Boiga irregularis ) has extirpated native...
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A New Portrait of a Potassium Pore
4 August 2005 (All day)
Researchers have deciphered the structure of a eukaryotic ion channel, an intricate structure that plays a central role in the firing of neurons. The new findings may settle some debates over how this critical protein operates.
Getting structures of the complex proteins that make up ion channels is no simple task. Researchers must first coax billions of copies of a protein to stack in a perfectly ordered crystal. They then fire a tight beam of x-rays at the crystal and track how those x-rays ricochet off the atoms to work out the atoms' positions. Two years ago, Roderick MacKinnon and colleagues at Rockefeller University in New York City attached antibody fragments to copies of a bacterial ion-channel protein to help stabilize it for structural analysis. But when the structure came out in a Nature paper in 2003, the position of the channel's voltage sensors--which tell neurons when to fire--didn't mesh with what many scientists had expected.
The new structure, described 5 August in Science, has experts breathing much easier. This time, MacKinnon's team was able to do away with the antibodies. The eukaryotic channels are nearly identical to those in bacteria, but there's a key difference: Eukaryotic potassium channels contain an additional protein domain, known as T1, and an another associated protein, known as β, that sit outside the cell membrane in the cytoplasm. With the help of some novel crystallization techniques that used lipids to crystallize the entire complex, MacKinnon's team found that T1 and β helped stabilize the channel protein during crystallization without requiring support from antibodies. Whether or not getting rid of the antibody fragments made the difference, the voltage sensors in the new structure are rotated upright, where other lines of evidence suggested they should be.
Like its bacterial predecessor, the new structure offers fresh insights into how the channel works. For one, says Richard Horn, a physiologist at Jefferson Medical College in Philadelphia, Pennsylvania, helices that form each voltage sensor aren't adjacent to those that help make up the pore--the channel through which potassium ions shuttle into and out of the cell. Rather, those domains interlace around one another. Gary Yellen, a neuroscientist at Harvard University in Cambridge, Massachusetts, adds that the new structure shows for the first time how the voltage sensor links to the pore, which, he says, "is a pretty neat thing to see."
Controversies remain. For example, ion-channel experts have long known that four positively charged arginine amino acids sit atop each of the voltage sensors that surround the pore. These charged arginines move in response to changes in the voltage across the cell membrane, pressing up and down on the lever that opens and closes the pore. But just how this movement takes place remains at issue.