New 3-D Image of 'Wasabi' Pain Receptor (Video)
/By Pat Anson, Editor
The spicy wasabi that gives a kick to the taste buds of sushi lovers may also be helping scientists develop new treatments for chronic pain.
Researchers at UC San Francisco say a protein in the human nervous system called the "wasabi receptor" -- because it helps us taste and smell spicy food -- also acts as a receptor to pain signals triggered by itching and inflammation.
They've created a 3-D image of wasabi receptor proteins -- officially known as TRPA1 -- which work as gatekeepers in sensory nerve cells. These gates, normally closed, open in response to strong chemical signals and allow ions to pass into the cell's interior, triggering a warning impulse.
"The pain system is there to warn us when we need to avoid things that can cause injury, but also to enhance protective mechanisms," said David Julius, PhD, professor and chair of UCSF's Department of Physiology, and co-senior author of a new study appearing online in the journal Nature.
"We've known that TRPA1 is very important in sensing environmental irritants, inflammatory pain, and itch, and so knowing more about how TRPA1 works is important for understanding basic pain mechanisms. Of course, this information may also help guide the design of new analgesic drugs."
The challenge for scientists is learning how and where the wasabi receptor is activated by chemical compounds. In theory, that would enable them to design a drug to alleviate pain by controlling the action of the ion channel -- in effect, shutting the gate.
Julius and his colleagues were able to capture images of TRPA1 that revealed its structure in three dimensions, including a cleft where an experimental drug molecule sits when it binds to the ion channel.
"A few drugs have been developed that target TRPA1, and in our 3-D structure we can see where one such drug binds," said Julius. "This provides important insight into how this one major class of drugs interacts with TRPA1 and thus how it may work to block channel function."
Researchers used a new imaging technique called electron cryo-microscopy (cryo-EM) to create an image of TRPA1 at a resolution of about 4 angstroms. By way of comparison, the thickness of a credit card is about 8 million angstroms.
The cryo-EM images of the TRPA1 ion channel are so refined they show it in three different states --closed, open, and partially open--a range that offers a lot of insight into how the channels work.
"Cryo-EM has undergone a 'resolution revolution' that has enabled us to literally see TRP channels in all their glory," said Julius. "We've had some idea what TRPA1 might look like, but there's something elegant and satisfying about obtaining the structure, because seeing really is believing."
