Contribution of the second transmembrane helix of the secretin receptor to the positioning of secretin

FEBS Lett. 1998 Mar 13;424(3):207-10. doi: 10.1016/s0014-5793(98)00175-6.


The secretin amino-terminal residues are essential for high affinity binding to its cognate receptor and for its biological activity. Mutation of the [Asp3] residue of secretin to [Asn3] decreased the ligand's affinity for the rat wild-type receptor 100-300-fold. Receptor mutations in the transmembrane 2 domain and the beginning of the first extracellular loop allowed the identification of three residues involved in recognition of the [Asp3] residue: D174, K173 and R166. Mutation of K173 and D174 not only reduced the secretin and [Asn3]secretin affinities, but also changed the receptor's selectivity as judged by a decreased secretin and [Asn3]secretin potency ratio. The most striking effect was observed when R166 was mutated to Q, D or L. This led to receptors with a very low affinity for secretin but an up to 10-fold higher affinity than the wild-type receptor for [Asn3]secretin. This suggested that R166, highly conserved in that subgroup of receptor, is a major determinant for the recognition of the [Asp3] of the ligand.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenylyl Cyclases / metabolism
  • Animals
  • Arginine
  • Binding Sites
  • Enzyme Activation
  • Mutation
  • Protein Conformation
  • Rats
  • Receptors, G-Protein-Coupled
  • Receptors, Gastrointestinal Hormone / chemistry*
  • Receptors, Gastrointestinal Hormone / genetics
  • Receptors, Gastrointestinal Hormone / metabolism*
  • Secretin / metabolism*


  • Receptors, G-Protein-Coupled
  • Receptors, Gastrointestinal Hormone
  • secretin receptor
  • Secretin
  • Arginine
  • Adenylyl Cyclases