Conformation of a peptide ligand bound to its G-protein coupled receptor

Nat Struct Biol. 2001 Feb;8(2):161-5. doi: 10.1038/84159.


Many peptide hormones elicit a wide array of physiological effects by binding to G-protein coupled receptors. We have determined the conformation of pituitary adenylate cyclase activating polypeptide, PACAP(1--21)NH(2), bound to a PACAP-specific receptor by NMR spectroscopy. Residues 3--7 form a unique beta-coil structure that is preceded by an N-terminal extended tail. This beta-coil creates a patch of hydrophobic residues that is important for receptor binding. In contrast, the C-terminal region (residues 8--21) forms an alpha-helix, similar to that in the micelle-bound PACAP. Thus, the conformational difference between PACAP in the receptor-bound and the micelle-bound states is limited to the N-terminal seven residues. This observation is consistent with the two-step ligand transportation model in which PACAP first binds to the membrane nonspecifically and then diffuses two-dimensionally in search of its receptor; a conformational change at the N-terminal region then allows specific interactions between the ligand and the receptor.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cell Line
  • Heterotrimeric GTP-Binding Proteins / metabolism*
  • Ligands
  • Micelles
  • Models, Biological
  • Models, Molecular
  • Molecular Sequence Data
  • Neuropeptides / chemistry*
  • Neuropeptides / genetics
  • Neuropeptides / metabolism*
  • Nuclear Magnetic Resonance, Biomolecular
  • Peptide Fragments / chemistry
  • Peptide Fragments / genetics
  • Peptide Fragments / metabolism
  • Pituitary Adenylate Cyclase-Activating Polypeptide
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide
  • Receptors, Pituitary Hormone / chemistry
  • Receptors, Pituitary Hormone / metabolism*
  • Sequence Deletion / genetics
  • Sheep
  • Spodoptera


  • Ligands
  • Micelles
  • Neuropeptides
  • Peptide Fragments
  • Pituitary Adenylate Cyclase-Activating Polypeptide
  • Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide
  • Receptors, Pituitary Hormone
  • Heterotrimeric GTP-Binding Proteins

Associated data

  • PDB/1GEA