Phosphoproteomics using Aurora columns helps identify mechanisms of conformational plasticity
G-protein-coupled receptors (GPCRs) are the largest and most diverse classes of membrane receptors in humans. These cell surface receptors act like the switchboard of the cell, communicating messages in the form of metabolites, light, peptides, lipids, sugars, and proteins. Such messages are critical for cells to survive and behave in a healthy fashion, and dysregulation of this messaging system can be causative for many diseases. Indeed, GPCRs are by far, the most therapeutically targeted class of proteins, with ~35% (>700) approved drugs targeting GPCRs both directly and indirectly.
Recent work published by Huang et. al. in Nature combined the use of Cryo-EM and phosphoproteomics to demonstrate the range of flexibility of these receptors, which is important in explaining the diverse sets of interactions they need to mediate their signals.
Structure of the neurotensin receptor 1 in complex with β-arrestin 1.
Nature. 2020 Mar;579(7798):303-308. doi: https://doi.org/10.1038/s41586-020-1953-1. Huang W, Masureel M, Qu Q, Janetzko J, Inoue A, Kato HE, Robertson MJ, Nguyen KC, Glenn JS, Skiniotis G, Kobilka BK.