Class-B GPCR activation: is ligand helix-capping the key?
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.
Neumann
Jean-Michel
JM
CEA, Institut de Biologie et Technologies de Saclay, URA CNRS 2096, Laboratoire des Protéines Membranaires, 91191Gif sur Yvette Cedex, France.
Couvineau
Alain
A
Murail
Samuel
S
Lacapère
Jean-Jacques
JJ
Jamin
Nadège
N
Laburthe
Marc
M
D000595:Amino Acid Sequence; D000818:Animals; D006801:Humans; D008024:Ligands; D008954:Models, Biological; D008969:Molecular Sequence Data; D011485:Protein Binding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry* / Q000378:metabolism*
D008024:Ligands; D043562:Receptors, G-Protein-Coupled