Transient Receptor Potential (TRP) ion channels are membrane proteins that play a role in the sensing of environmental and cellular signals. In a recent article in Nature, (Liao et. al.)**, researchers report that they have solved the 3D structure of the TRPV1 ion channel to a near-atomic resolution (3.4 Angstroms) using cryo electron microscopy (cryo-EM) employing a Gatan K2 SummitTM electron counting camera. This marks the first time that the detailed structure of a member of the large and diverse TRP channel family has been solved.
“Ion channels are among the highest potential targets for drug development. Understanding these channels at atomic resolution speeds up the development of powerful therapeutics that modulate the activity of these channels”, says Dr. Christopher Booth, Life Science Product Manager at Gatan. “Until now the 3D structure of ion channels could only be solved using 2D or 3D crystallography, which often required years of painstaking effort to create crystalline samples. This trail blazing work shows that near atomic-resolution structural biology research is now possible without the need for crystallization.”
Shown above are some examples illustrating the remarkable reconstruction quality that can be achieved in single particle cryo-EM using the high contrast, low noise K2 Summit electron counting camera. The density map on the left allows for the unequivocal tracing of the polypeptide backbone de novo revealing the 3D location of each atom in this protein.
“Our team has been trying to solve this structure using X-ray crystallography for several years, but we were never able to crystallize the TRPV1 proteins to undertake these kinds of experiments.” says David Julius, professor of physiology at the University of California, San Francisco (UCSF).
This is the first time we’ve been able to resolve side chains in membrane proteins without crystallization”, says Yifan Cheng, associate professor of biochemistry and biophysics at UCSF. “It shows that single-particle cryo-EM can now be used to solve small, low symmetry particles at the highest resolution, and that cryo-EM is applicable to some of the most difficult specimens.”
“This benchmark result is proof that the Gatan K2 Summit electron counting camera is revolutionizing structural biology”, states Dr. Sander Gubbens, Gatan’s President. “We are immensely proud that our K2 Summit camera is dramatically expanding the field of cryo-EM and enabling truly novel research.”
The K2 Summit is the result of a very successful collaboration between scientists at Gatan, the University of California San Francisco, and the Lawrence Berkeley National Laboratory, with partial funding from the Howard Hughes Medical Institute and the National Science Foundation through an American Recovery and Reinvestment Act Major Instrumentation grant.
** Liao M., Cao E., Julius D., Cheng Y., Structure of the TRPV1 ion channel determined by electron cryo-microscopy. Nature, 504 pp.107-112. doi:10.1038/nature12822.