Variable G protein determinants of GPCR coupling selectivity
Year: 2019
Type: article
Abstract: Significance G protein-coupled receptors (GPCRs) regulate a wide variety of important cellular processes and are targeted by a large fraction of approved drugs. GPCRs signal by activating heterotrimeric G proteins and must couple to a select subset of G proteins to produce appropriate intracellular responses. It is not known how GPCRs select G proteins, but it is generally accepted that the Gα subunit C terminus is the primary G protein determinant of coupling selectivity. We systematically studied coupling of GPCRs to four families of G proteins and chimeras with C terminal regions that were exchanged between families. We uncovered rules for coupling selectivity and found that different GPCRs can recognize different features of the same G protein for selective coupling.
Institutions: Augusta University, Beckman Research Institute, Tohoku University
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Awards: G1088328575, Structural dynamics underlying GPCR-G protein selectivity, G4266663313, Contributions of Gα Subunit Distal Helix 5 to GPCR-G Protein Selectivity, G5161907583, G5347732863, Signaling basis of GPCR-acting drugs and their therapeutic mechanisms, Direct assessment of GPCR-transducer coupling and G protein subtype bias, G8601547617, G877601775
OpenAlex ID: W2947163054