K2 Summit camera enables scientists to break the 3 Å barrier in structural biology using cryo-electron microscopy (cryo-EM)

Posted: 
April 15, 2015

For many years the lack of sub 3 Å (angstrom) high-resolution structures solved by single particle cryo-electron microscopy (cryo-EM) created speculation that 3 Å might be the fundamental resolution limit of the technique. Now, in two papers, scientists using the Gatan K2 Summit® direct detection camera end the speculation by breaking through this 3 Å barrier. The super-resolution K2 Summit camera uses electron counting to record the highest resolution images with the lowest noise. High-resolution structures that were formerly only accessible by x-ray crystallography can now be solved by the K2 Summit camera.

Cryo-EM has the unique advantage of being able to study large complexes in solution rather than in a protein crystal, allowing the characterization of heterogeneous or flexible protein complexes. High-resolution cryo-EM can, therefore, provide information about protein dynamics, which is key to understanding the functions of many macromolecular complexes.

This advantage of cryo-EM is of major interest to the pharmaceutical industry. However, for pharma to adopt cryo-EM in its structure-based drug design, cryo-EM had to reach resolutions higher than 3 Å. The research article 2.8 Å resolution reconstruction of the Thermoplasma acidophilum 20 S proteasome using cryo electron microscopy, eLife 2015;10.7554/eLife.06380, demonstrates that with the help of the K2 Summit camera, single-particle cryo-EM can compete with x-ray crystallography to determine protein structures for rational drug design at 2.8 Å resolution. At this resolution it is possible to uniquely identify the rotameric conformation adopted by some amino-acid side chains (rotamers) and resolve ordered water molecules.

“We are thrilled that our K2 Summit camera is once again enabling scientists to push the frontiers of science,” said Sander Gubbens, President of Gatan. “The results definitively show that 3 Å is not a fundamental resolution limit of cryo-EM, and we are pleased that our K2 Summit camera enabled scientists to finally and convincingly push past this perceived barrier.”

In another recently published paper, Atomic structure of anthrax protective antigen pore elucidates toxin translocation, Nature 2015, 10.1038/nature14247, the research team, using a K2 Summit camera, were able to determine a protective antigen pore structure at 2.9 Å resolution. The structure reveals the long-sought-after catalytic phi-clamp and the membrane spanning translocation channel, and supports the Brownian ratchet model for protein translocation.

 “These breakthroughs are part of a consistent trend with structural biologists beginning to consider alternatives to x-ray crystallography,” stated Chris Booth, Life Science Product Manager at Gatan. “The K2 Summit is making it possible to solve these structures without having to go to all the effort of crystallizing the protein.”

For more information regarding the K2 camera, please visit: http://www.gatan.com/k2

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About Gatan Inc.

Gatan, Inc. is the world's leading manufacturer of instrumentation and software used to enhance and extend the operation and performance of electron microscopes. Gatan products, which are fully compatible with nearly all electron microscope models, cover the entire range of the research process—from specimen preparation and manipulation to imaging and analysis. The Gatan brand name is recognized and respected throughout the worldwide scientific community and has been synonymous with high quality products and leading technology for more than 50 years. Gatan is headquartered in Pleasanton, California, U.S.A. For more information, visit: www.gatan.com.

 

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Jennifer McKie
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