Pushing the boundaries of cryo-EM for GPCRs

Presenter: Professor Radostin Danev
Advanced Structural Studies
Graduate School of Medicine
The University of Tokyo
Cryo-electron microscopy (cryo-EM) continues to grow as a powerful method for structural studies ofbiomolecules and their complexes. Nowadays, it can routinely determine molecular structures withresolutions in the 2.5 - 3.5 Å range. Such results are adequate for modelling of the protein but lackfidelity for confident localization of water molecules and hydrogen atoms. Unambiguous elucidation ofthe biochemistry behind protein function and pharmacology of drugs would require atomic resolutionstructures, at levels below 1.5 Å. Last year, several groups worldwide demonstrated atomic resolutioncryo-EM with a test sample comprising the “easy” soluble protein apoferritin. This was an importanttechnological milestone showcasing the best-case-scenario capabilities of cryo-EM. However,membrane proteins, and other real-world samples, impose numerous experimental challenges, suchas small size, heterogeneity, flexibility, preferential orientation, etc. The talk will be about optimizingthe performance of cryo-EM for challenging membrane proteins, and particularly in studies of thestructure, pharmacology, and dynamics of G protein-coupled receptors.
About Professor Rado Danev:
Rado Danev graduated solid-state physics at the University ofSofia in Bulgaria. During his Ph.D., and in the following years, he worked on the development of phase plates for electron microscopy in the laboratory of Prof. Nagayama in Okazaki, Japan. He published the first phase plate applications in cryo-EM single particle analysis and cryo-tomography. In 2011 he became a group leader at the Max Planck Institute ofBiochemistry in Martinsried, Germany, and in the same year was awarded the Burton Medal of the Microscopy Society ofAmerica. Thereafter, he led an academia-industry collaboration
that resulted in the development of the Volta phase plate (VPP). For this research, in 2017 he was awarded the Ernst Ruska prize of the German Society for Electron Microscopy. Since November 2018, Rado is a professor at the Graduate School of Medicine, The University of Tokyo. His current projects involve cryo-EM studies of GPCRs in collaboration with the GPCR team at Monash University, first forays into cryo-tomography, and more generally methods development for cryo-EM.
Chair: Isabella Russell, Monash PhD student