Receptor deciphered

Credit: courtesy of Jayasankar Jasti, Hiroyasu Furukawa, Eric B. Gonzales, Eric Gouaux The paper: E. Gouaux et al. "Structure of acid-sensing ion channel 1 at 1.9 Å resolution and low pH,"

By | February 1, 2009

<figcaption> Credit: courtesy of Jayasankar Jasti, Hiroyasu Furukawa, Eric B. Gonzales, Eric
                    Gouaux</figcaption>
Credit: courtesy of Jayasankar Jasti, Hiroyasu Furukawa, Eric B. Gonzales, Eric Gouaux

The paper:

E. Gouaux et al. "Structure of acid-sensing ion channel 1 at 1.9 Å resolution and low pH," Nature, 449:316-23, 2007. (Cited in 68 papers)

The finding:

Neuroscientist Eric Gouaux's team at Oregon Health and Science University provided the first ever high-resolution snapshot of the acid sensing ion channel (ASIC), a proton-activated sodium channel involved in the processing of sensory information. They expressed one of six isoforms of the channel, ASIC1, in cell culture, performed crystallography and electrophysiology, solving the structure at 1.9 Å resolution which revealed the shape and location of proton-binding sites on the channel.

The surprise:

Unlike other ion channels, which are comprised of four to six subunits, Gouaux says he was shocked to discover that ASIC1 was made of only three subunits. "It was unlike any other ion channel that's ever been seen before," Gouaux says. The image also revealed ASICs had a large extracellular domain, contributing to control of the channel.

The follow up:

"It was like a big black box and now we have a picture of it," says Cecilia Canessa from Yale University. Her group is interested in what the structure of ASIC1 can teach scientists about the closely related epithelial sodium channel (ENaC), which is essential for sodium homeostasis in mammals.

The application:

Researchers believe understanding the gating mechanisms of ASIC could lead to small molecule channel blocker therapies to treat pain, cystic fibrosis, and prevent ischemic cell death as a consequence of stroke.

No. of subunitsLocation of channel domain
Acid-sensing ion channel 3 Extracellular
Glutamate receptors 4 Extracellular
Gap junctions 6 Intracellular

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