Solving molecular puzzles in GPCR signaling with cryo-EM

Cryo-EM has revolutionized structural studies of G protein-coupled receptors over the past few years. More facile structure determination of active GPCRs has enabled the field to understand the molecular basis of receptor function at an unprecedented pace. I will discuss our efforts to use cryo-EM structure determination to interrogate GPCRs that remain orphan or otherwise poorly understood. We envision that cryo-EM-enabled structures of transmembrane proteins will usher in a new era of structural biology as a hypothesis generating tool for the dark matter of the proteome.