Passing the baton in class B GPCRs: peptide hormone activation via helix induction?

Trends Biochem Sci. 2009 Jun;34(6):303-10. doi: 10.1016/j.tibs.2009.02.004. Epub 2009 May 14.


G-protein-coupled receptors (GPCRs) represent the largest constellation of validated drug targets. Crystal structures of class A GPCRs have facilitated major advances in understanding the principles underlying GPCR activation. By contrast, relatively little is known about class B GPCRs, a family of receptors for a variety of therapeutically relevant peptide hormones. Encouraging progress has recently been made through the structural elucidation of several extracellular hormone-binding domains of class B GPCRs in complex with their natural ligands or synthetic analogues. The structures reveal similar modes of ligand binding, with concomitant alpha-helical structuring of the ligand. The latter suggests an attractive mechanical model for class B GPCR activation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Humans
  • Ligands
  • Models, Biological
  • Molecular Sequence Data
  • Peptide Hormones / metabolism*
  • Peptides / chemistry
  • Protein Conformation
  • Protein Folding
  • Protein Structure, Secondary
  • Receptors, G-Protein-Coupled / chemistry*
  • Receptors, G-Protein-Coupled / physiology*
  • Sequence Homology, Amino Acid


  • Ligands
  • Peptide Hormones
  • Peptides
  • Receptors, G-Protein-Coupled