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Impact of the DRY Motif and the Missing "Ionic Lock" on Constitutive Activity and G-Protein Coupling of the Human Histamine H-4 Receptor

Schneider, Erich H. ; Schnell, David ; Strasser, Andrea ; Dove, Stefan ; Seifert, Roland



Abstract

It is assumed that many G protein-coupled receptors (GPCRs) are restrained in an inactive state by the "ionic lock," an interaction between an arginine in transmembrane domain (TM) 3 (R3.50) and a negatively charged residue in TM6 (D/E6.30). In the human histamine H-4 receptor (hH(4)R), alanine is present in position 6.30. To elucidate whether this mutation causes the high constitutive activity ...

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