Identification of a critical aspartate residue in transmembrane domain three necessary for the binding of somatostatin to the somatostatin receptor SSTR2

Biochem Biophys Res Commun. 1995 Nov 22;216(3):913-21. doi: 10.1006/bbrc.1995.2708.


To determine which residues within the rat somatostatin receptor subtype SSTR2 may be interacting with the lys9 of somatostatin-14 (S-14), mutant SSTR2 receptors were created by mutating asp89 or asp122. [125I Tyr11]S-14 binding to D89A and D89E mutants suggests that asp89 is not directly involved in S-14 binding. Binding studies with the charge switch mutants, asp9S-14, and D122K, suggest that asp122 may be interacting with the lys9 of S-14. [125I Tyr11]asp9S-14 displayed saturable binding to D122K with an affinity comparable to that seen with [125I Tyr11]S-14 and WT SSTR2. These data suggest that the interaction between lys9 of S-14 and the TM3 asp122 of SSTR2 represents one contact site between S-14 and SSTR2.

MeSH terms

  • Animals
  • Aspartic Acid / analysis*
  • Aspartic Acid / metabolism
  • Binding Sites
  • Binding, Competitive
  • CHO Cells
  • Cell Membrane / chemistry*
  • Cricetinae
  • Guanosine 5'-O-(3-Thiotriphosphate) / pharmacology
  • Hormone Antagonists / metabolism
  • Mutagenesis, Site-Directed
  • Peptides, Cyclic / metabolism
  • Rats
  • Receptors, Somatostatin / chemistry*
  • Receptors, Somatostatin / genetics
  • Receptors, Somatostatin / metabolism*
  • Somatostatin / metabolism*
  • Structure-Activity Relationship
  • Transfection
  • Tyrosine / metabolism


  • Hormone Antagonists
  • Peptides, Cyclic
  • Receptors, Somatostatin
  • Aspartic Acid
  • Guanosine 5'-O-(3-Thiotriphosphate)
  • Tyrosine
  • Somatostatin
  • seglitide