Structural Basis of Dopamine Receptor Activation

Part of the The Receptors book series (REC)


G protein-coupled receptors (GPCRs) are seven transmembrane (TM) proteins representing the largest and most universally expressed cell surface receptors and are present in almost all species and in a wide variety of cells. Here we will focus our attention on the catecholamine-binding GPCRs and in particular on the dopamine receptors. The catecholamine-binding GPCRs form a group of rhodopsin-like GPCRs composed of adrenoceptors, which are endogenously activated by epinephrine and norepinephrine, and dopamine receptors. We review the different “molecular switches” involved in GPCR activation and we emphasize the importance of extracellular loop 2 (ECL2) in ligand binding. A better understanding of the functional role of ECL2 can be achieved after the release of the crystal structures of B2AR and rhodopsin, which are consistent with dopamine D2 receptor substituted cysteine accessibility method (SCAM) experimental data. Even though reconstituted GPCR monomers appear sufficient to activate a G protein, in the native setting their dimerization/oligomerization may modulate activation through changes at the dimerization interface or a larger-scale reorientation of the protomers. Therefore, the structural aspects of oligomerization and their importance for receptor activation and signaling are also addressed.


Catecholamine-binding GPCRs Dopamine receptors Binding site ECL2 GPCR oligomerization GPCR–G Protein interaction Activation Structural rearrangements 


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Copyright information

© Humana Press, a part of Springer Science+Business Media, LLC 2010

Authors and Affiliations

  1. 1.Department of Physiology and BiophysicsWeill Medical College of Cornell UniversityNew YorkUSA
  2. 2.Department of Physiology and Biophysics and Institute for Computational BiomedicineWeill Medical College of Cornell UniversityNew YorkUSA
  3. 3.Department of PsychiatryColumbia University College of Physicians and SurgeonsNew YorkUSA
  4. 4.Department of Physiology and Biophysics and the HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational BiomedicineWeill Medical College of Cornell UniversityNew YorkUSA
  5. 5.Center for Molecular RecognitionColumbia University College of Physicians and SurgeonsNew YorkUSA

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