Open and Shut: Pain Signals in Nerve Cells

ASICAa protein changing from open to closed postions — As the proton concentration increases or decreases, the gated channel ASIC1a toggles between open and closed positions, controlling the timing of signals traveling through the cell membrane of one neuron en route to the next.

Using protein crystallography at the Advanced Light Source (ALS), investigators at Oregon Health and Science University visualized an acid-sensing ion channel, ASIC1a, in it’s elusive closed state for the first time. An important cell membrane protein in the central nervous system, ASIC1a plays a role in sensing pain and in forming memories of fear. The researchers used protein crystals of ASIC1a channels purified in the closed state and compiled X-ray data from ALS Beamline 5.0.2 and the Advanced Photon Source at Argonne National Lab to build a model of the closed channel structure. Defining the closed structure enabled the researchers to generate a comprehensive molecular model of how ASIC1a toggles between the closed, open, and desensitized states.

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