Abstract
Class B GPCRs (G-protein-coupled receptors) share heptahelical topology and G-protein binding with other superfamily members, yet have unique structures and modes of activation. Natural ligands for these receptors are moderate-length peptides with C-terminal α-helices. NMR and crystal structures of the peptidebound disulfide-bonded receptor N-terminal domains demonstrate that these helices occupy a conserved groove; however, the details of this interaction vary from one receptor to another. In this review, we focus on the prototypic secretin receptor and use extensive intrinsic photoaffinity labelling, structure-activity series, alanine-replacement mutagenesis and fluorescence analysis to define the molecular basis for this interaction. Additionally, experimental validation of predictions coming from in silico molecular modelling has provided a basis for enhancement of binding affinity. Such insights will be useful in the rational development of drugs acting at this important group of targets.
Original language | English (US) |
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Pages (from-to) | 154-158 |
Number of pages | 5 |
Journal | Biochemical Society Transactions |
Volume | 41 |
Issue number | 1 |
DOIs | |
State | Published - Feb 2013 |
Keywords
- GPCR (G-protein-coupled receptor)
- Ligand binding
- Receptor conformation
ASJC Scopus subject areas
- Biochemistry