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A MicroED Solution to the Lens MP20 Enigma

My laboratory studies the structures of membrane proteins that are important in maintaining cellular homeostasis. Understanding structure (and hence function) requires scientists to build an atomic resolution map of every atom in the protein of interest, that is, an atomic structural model of the protein of interest captured in various functional states. In 2013 we unveiled the method Microcrystal Electron Diffraction (MicroED) and demonstrated that it is feasible to determine high-resolution protein structures by electron crystallography of three-dimensional crystals in an electron cryo-microscope (CryoEM). The CryoEM is used in diffraction mode for structural analysis of proteins of interest using vanishingly small crystals. In this seminar I will describe our efforts in the MicroED field and illustrate how this technique allows us to determine structures for novel proteins that were beyond the reach of other methods. I will use the small membrane protein MP20 from the eye lens as a case study and reveal an unexpected role for this protein as a tight junction protein.

Biography

Tamir Gonen, PhD, is a membrane biophysicist and an expert in crystallography and cryo EM. Gonen is a professor of Biological Chemistry and Physiology at the David Geffen School of Medicine of the University of California, Los Angeles and an Investigator of the Howard Hughes Medical Institute. Gonen obtained his advanced degree from the University of Auckland in New Zealand then postgraduate training at Harvard Medical School. He established his independent career first at the University of Washington School of Medicine, then at the Howard Hughes Medical Institute Janelia Research Campus and finally at UCLA School of Medicine. Gonen served on several study sections of the National Institutes of Health and acted as ad hoc reviewer for several international funding agencies. Dr. Gonen is best known for his research on the structure of membrane proteins and for leading method development in structural biology. He spearheaded the technology development of Microcrystal Electron Diffraction (MicroED) as a new method for structural biology. With this method Dr Gonen has pushed the boundaries of cryoEM and determined several previously unknown structures at sub-atomic resolutions. Gonen authored nearly 200 publications and several of his past trainees are now faculty around the world at top universities. Among his accolades, Dr Gonen was a recipient of a Career Development Award from the American Diabetes Association and an Early Career Scientist award from the Howard Hughes Medical Institute. Gonen was awarded a Technology & Innovation Award from Thermo Fisher, the A. L. Patterson Award from the American Crystallographic Association and more recently the Carl Branded award from the Protein Society. Finally, Gonen is also a Member of the Royal Society of New Zealand.