Blueprint of body's heat sensor discovered

Scientists have discovered the structure of a protein linked to pain and heat perception, which plays a role in maintaining a healthy heart, helping dispose of pathogens and inducing cell death in some cancers.
The port-like structure is an ion channel in the cell surface membrane called TRPV2.
"These receptors are gaining particular attention because they are so critical to how we sense and respond to our environment," said Seok-Yong Lee from Duke University in US.
"Our results give a hint as to how one receptor works, a necessary component for developing new treatments for a variety of conditions involving sensation," Lee added.

Ion channels are scattered across all cell membranes and act as gatekeepers of information flowing in and out of cells. In the case of TRPV (Transient Receptor Potential Vanilloid), this information takes the form of calcium ions.
Like the turning of a valve, TRPV receptors open in response to noxious heat or other stimuli, allowing an influx of calcium ions that convey a signal through the nervous system to the brain.

Deducing the schematics of these valves can give the blueprint for designing drugs that target ion channels, researchers said.
Unlike TRPV1, which is only found in the nervous system, TRPV2 is present throughout the body and has been implicated in a variety of human conditions, including heart disease, the immune response, and cancer, they said.

It took researchers several years to work out the right conditions to keep the protein well dispersed and stable in biochemical solution, so it could be flash frozen and visualised by a technique known as cryo-electron microscopy.
Gabriel Lander, a biologist at the Scripps Research Institute in California used this technique to determine the structure of TRPV2 at near-atomic resolution.
Cryo-electron microscopy works much like regular electron microscopy - electrons are shot at the sample, refracting or bouncing back from dense areas and passing through empty ones.
Lander took about half a million 2D images, which he then ran through a sophisticated computer programme to generate a 3D picture of the protein.

When researchers compared the structure of TRPV2 to TRPV1, they found that it did not fit the mold for either the open or closed confirmation of the closely related protein.
Rather, it seemed to inhabit an in-between stage, suggesting a third state where the channel becomes desensitised to repeated stimuli, much like a person might get used to the beeps of a faulty smoke detector.
Researchers believe that that studying this desensitised state could point to a way to alleviate chronic pain in people.
The findings were published in the journal Nature Structural and Molecular Biology.