Article
A structural basis for how ligand binding site changes can allosterically regulate GPCR signaling and engender functional selectivity.
Science signaling - 4 Feb 2020
Sanchez-Soto Marta, Verma Ravi Kumar, Willette Blair K A, Gonye Elizabeth C, Moore Annah M, Moritz Amy E, Boateng Comfort A, Yano Hideaki, Free R Benjamin, Shi Lei, Sibley David R
Abstract excerpt
Signaling bias is the propensity for some agonists to preferentially stimulate G protein-coupled receptor (GPCR) signaling through one intracellular pathway versus another. We previously identified a G protein-biased agonist of the D2 dopamine receptor (D2R) that results in impaired β-arrestin recruitment. This signaling bias was predicted to arise from unique interactions of the ligand with a hydrophobic pocket...
Topics
- Amino Acid Sequence
- Animals
- Binding Sites
- CHO Cells
- Cricetinae
- Cricetulus
- GTP-Binding Proteins
- HEK293 Cells
- Humans
- Ligands
- Models, Molecular