Interruption of the ionic lock in the bradykinin B2 receptor results in constitutive internalization and turns several antagonists into strong agonists

• Published in: The Journal of pharmacology and experimental therapeutics Vol. 344; no. 1; pp. 85 - 95
• Main Authors: Leschner, Jasmin, Wennerberg, Goeran, Feierler, Jens, Bermudez, Marcel, Welte, Benjamin, Kalatskaya, Irina, Wolber, Gerhard, Faussner, Alexander
• Format: Journal Article
• Language: English
• Published: United States 01.01.2013
• Subjects: Amino Acids - metabolism; Biotinylation; Bradykinin - metabolism; Bradykinin B2 Receptor Antagonists; Gene Expression; GTP-Binding Proteins - metabolism; HEK293 Cells; Humans; Hydrolysis; Inositol Phosphates - metabolism; Ions - metabolism; Phosphorylation; Point Mutation; Pyridones - pharmacology; Quinolines - pharmacology; Receptor, Bradykinin B2 - agonists; Receptor, Bradykinin B2 - drug effects; Receptors, G-Protein-Coupled - drug effects; Receptors, G-Protein-Coupled - metabolism; Temperature

The DRY motif with the highly conserved R3.50 is a hallmark of family A G protein-coupled receptors (GPCRs). The crystal structure of rhodopsin revealed a salt bridge between R135(3.50) and another conserved residue, E247(6.30), in helix 6. This ionic lock was shown to maintain rhodopsin in its inac...