Key Drug Target Shown Assembling in Real Time
The activation of G proteins by G protein-coupled receptors (GPCRs) underlies the majority of transmembrane signaling by hormones and neurotransmitters.
In an effort to better understand the structural basis of coupling specificity, researchers used time-resolved structural mass spectrometry techniques to investigate GPCR-G protein complex formation and G-protein activation. The techniques revealed the timeline for different parts of GPCR interacting with its signaling partners.
The results suggest that coupling specificity is determined by one or more transient intermediate states that serve as selectivity filters and precede the formation of the stable nucleotide-free GPCR-G protein complexes observed in crystal and cryo-EM structures.
Y. Du, N. M. Duc, S. G.F. Rasmussen, D. Hilger, X. Kubiak, L. Wang, J. Bohon, H. R. Kim, M. Wegrecki, A. Asuru, K. M. Jeong, J. Lee, M. R. Chance, D. T. Lodowski, B. K. Kobilka, K. Y. Chung, “Assembly of a GPCR-G Protein Complex,” Cell 177:5 1232-1242 (2019). [DOI: 10.1016/j.cell.2019.04.022]