Cryo-electron microscopy (cryo-EM), in which biological samples are flash frozen and then visualized with an electron microscope, offers scientists a nearly atomic-level glimpse of proteins in their native state. For a long time, the technique's advantages were offset by its limited resolution compared to x-ray crystallography, a more traditional method of determining protein structures.
But Yifan Cheng's innovations have amplified cryo-EM's potential beyond what was once thought possible, enabling his lab and others to discern detailed structural information for proteins that are difficult to study with x-ray crystallography.
In 2013, Cheng's lab developed an algorithm to correct for motion-induced blurring in images, allowing users to take full advantage of sensitive new electron detectors and obtain high-resolution information from their samples. With this and other technical advances, Cheng and his collaborators in the David Julius lab (University of California, San Francisco) are revealing the structures of proteins so small and asymmetrical that many thought they could not be studied using cryo-EM.
Their structures of TRPV1, an ion channel embedded in the membranes of nerve cells that detects temperature changes and the pungent chile-pepper component capsaicin, show three different conformations of the protein with atomic-level detail. As the first such structures for any transient receptor potential (TRP) channel, they provide a blueprint for understanding this large, diverse family of proteins.