Wednesday, December 6, 2023
Mitochondrial Health

Richard Henderson: How Aaron's seminal work led to the resolution revolution in cryoEM

Aaron Klug: A Scientific Retrospective
How Aaron’s seminal work led to the resolution revolution in cryoEM by Richard Henderson

Aaron Klug was instrumental in revealing the structures of complex biological molecules, from viruses to tRNA, to chromatin and zinc fingers. His most important contribution to scientific research was the development of crystallographic electron microscopy: combining the techniques of electron microscopy and X-ray diffraction to recover three-dimensional structural information from two-dimensional electron micrographs. For this work he was the sole recipient of the 1982 Nobel Prize in Chemistry.

Richard Henderson is a structural biologist, with a physics background from Edinburgh University. After a PhD at the LMB working on enzyme mechanisms, he developed an interest in membrane proteins as a postdoc at Yale.

Back at the LMB with Nigel Unwin, he used electron microscopy to determine the structure of bacteriorhodopsin in two-dimensional crystals, first at low resolution and later at atomic resolution. Then, with Chris Tate, he helped to develop the method of “conformational thermostabilisation” that allows any membrane protein to be made more stable while at the same time retaining a chosen conformation of interest. This helped the crystallisation and structure determination of several G protein–coupled receptors (GPCRs) and led to the founding of the MRC start-up company Heptares in 2007, which is now wholly owned by the Japanese company Sosei, developing new drugs for medically important GPCRs.

For the last 20 years, Richard has been working to improve the methodology of single particle electron cryomicroscopy (cryo-EM), which has recently reached the stage where it is possible to obtain atomic structures of a wide variety of macromolecular complexes routinely without crystals. He is now focused on solving the remaining problems in cryo- EM so the method can reach its theoretical potential.

About the MRC Laboratory of Molecular Biology (LMB): The LMB is one of the world’s leading research institutes. Discoveries and inventions developed at the LMB, for example DNA sequencing and methods to determine the structure of proteins, have revolutionised all areas of biology. Its scientists work to advance understanding of biological processes at the molecular level. This information will help us to understand the workings of complex systems, such as the immune system and the brain, and solve key problems in human health.
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