Abstract: 

G-protein coupled receptors (GPCRs) are one of the largest families of membrane protein receptors in the human genome and play critical roles in countless cellular systems in the human body.  Tremendous interest exists into exploiting these promising and attractive drug targets using structure-based drug design approaches.  With recent advancements in electron cryo-microscopy (cryo-EM) and modern innovations in GPCR biochemistry we enter a second era of GPCR structural biology focused on agonist bound complexes.  Differing from the first era centered on lipidic cubic phase X-ray crystallography of typically antagonist bound uncoupled states.  Here I will present some of my lab’s research aimed at improving methodologies to expedite automated single particle data collection at 200 keV.  High-resolution, high-speed data collection methodological improvements have enabled my lab to solve over 50 agonist bound high-resolution G protein bound structures to-date in collaborations with Dr. Roth’s Lab.  In this talk, I will also highlight some recent structural insights into an orphan GPCR family involved in itch and recent work on understanding serotonin receptors.