Class-B GPCR activation: is ligand helix-capping the key?

Trends Biochem Sci. 2008 Jul;33(7):314-9. doi: 10.1016/j.tibs.2008.05.001. Epub 2008 Jun 12.


The class B family of G-protein-coupled receptors (GPCRs) regulates essential physiological functions such as exocrine and endocrine secretions, feeding behaviour, metabolism, growth, and neuro- and immuno-modulations. These receptors are activated by endogenous peptide hormones including secretin, glucagon, vasoactive intestinal peptide, corticotropin-releasing factor and parathyroid hormone. We have identified a common structural motif that is encoded in all class B GPCR-ligand N-terminal sequences. We propose that this local structure, a helix N-capping motif, is formed upon receptor binding and constitutes a key element underlying class B GPCR activation. The folded backbone conformation imposed by the capping structure could serve as a template for a rational design of drugs targeting class B GPCRs in several diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Humans
  • Ligands
  • Models, Biological
  • Molecular Sequence Data
  • Protein Binding
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Receptors, G-Protein-Coupled / chemistry*
  • Receptors, G-Protein-Coupled / metabolism*


  • Ligands
  • Receptors, G-Protein-Coupled