Structure of a beta1-adrenergic G-protein-coupled receptor

Nature. 2008 Jul 24;454(7203):486-91. doi: 10.1038/nature07101. Epub 2008 Jun 25.


G-protein-coupled receptors have a major role in transmembrane signalling in most eukaryotes and many are important drug targets. Here we report the 2.7 A resolution crystal structure of a beta(1)-adrenergic receptor in complex with the high-affinity antagonist cyanopindolol. The modified turkey (Meleagris gallopavo) receptor was selected to be in its antagonist conformation and its thermostability improved by earlier limited mutagenesis. The ligand-binding pocket comprises 15 side chains from amino acid residues in 4 transmembrane alpha-helices and extracellular loop 2. This loop defines the entrance of the ligand-binding pocket and is stabilized by two disulphide bonds and a sodium ion. Binding of cyanopindolol to the beta(1)-adrenergic receptor and binding of carazolol to the beta(2)-adrenergic receptor involve similar interactions. A short well-defined helix in cytoplasmic loop 2, not observed in either rhodopsin or the beta(2)-adrenergic receptor, directly interacts by means of a tyrosine with the highly conserved DRY motif at the end of helix 3 that is essential for receptor activation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic beta-1 Receptor Agonists
  • Adrenergic beta-1 Receptor Antagonists
  • Adrenergic beta-Antagonists / chemistry
  • Adrenergic beta-Antagonists / metabolism
  • Amino Acid Motifs
  • Animals
  • Binding Sites
  • Crystallization
  • Crystallography, X-Ray
  • Ligands
  • Models, Molecular
  • Mutant Proteins / chemistry
  • Mutant Proteins / genetics
  • Mutant Proteins / metabolism
  • Mutation
  • Pindolol / analogs & derivatives
  • Pindolol / chemistry
  • Pindolol / metabolism
  • Propanolamines / chemistry
  • Propanolamines / metabolism
  • Protein Conformation
  • Receptors, Adrenergic, beta-1 / chemistry*
  • Receptors, Adrenergic, beta-1 / metabolism
  • Thermodynamics
  • Turkeys


  • Adrenergic beta-1 Receptor Agonists
  • Adrenergic beta-1 Receptor Antagonists
  • Adrenergic beta-Antagonists
  • Ligands
  • Mutant Proteins
  • Propanolamines
  • Receptors, Adrenergic, beta-1
  • carazolol
  • cyanopindolol
  • Pindolol

Associated data

  • PDB/2VT4