Passing the baton in class B GPCRs: peptide hormone activation via helix induction?
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.
Parthier
Christoph
C
Institut für Biochemie und Biotechnologie, Martin-Luther-Universität Halle-Wittenberg, Kurt-Mothes-Strasse 3, D-06120 Halle (Saale), Germany. parthier@biochemtech.uni-halle.de
Reedtz-Runge
Steffen
S
Rudolph
Rainer
R
Stubbs
Milton T
MT
D000595:Amino Acid Sequence; D000818:Animals; D006801:Humans; D008024:Ligands; D008954:Models, Biological; D008969:Molecular Sequence Data; D036361:Peptide Hormones / Q000378:metabolism*; D010455:Peptides / Q000737:chemistry; D011487:Protein Conformation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry* / Q000502:physiology*; D017386:Sequence Homology, Amino Acid
D008024:Ligands; D036361:Peptide Hormones; D010455:Peptides; D043562:Receptors, G-Protein-Coupled