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CCeMMP Seminar Series – Prof. Radostin Danev November 2021

Using cryo-EM to interrogate the structure and dynamics of GPCRs

Cryo-electron microscopy (cryo-EM) continues to grow as a powerful method for structural studies of biomolecules and their complexes. Nowadays, it can routinely determine molecular structures with resolutions in the 2.5 – 3.5 Å range. Such results are adequate for modelling of the protein but lack fidelity for confident localization of water molecules and hydrogen atoms. Unambiguous elucidation of the biochemistry behind protein function and pharmacology of drugs would require atomic resolution structures, at levels below 1.5 Å. Last year, several groups worldwide demonstrated atomic resolution cryo-EM with a test sample comprising the “easy” soluble protein apoferritin. This was an important technological milestone showcasing the best-case-scenario capabilities of cryo-EM. However, membrane proteins, and other real-world samples, impose numerous experimental challenges, such as small size, heterogeneity, flexibility, preferential orientation, etc.

Prof. Radostin Danev

Advanced Structural Studies

Graduate School of Medicine, The University of Tokyo