Glutamate 301 of the mouse gonadotropin-releasing hormone receptor confers specificity for arginine 8 of mammalian gonadotropin-releasing hormone.

摘要: The Arg residue at position 8 of mammalian GnRH is necessary for high affinity binding to receptors. This requirement has been postulated derive from an electrostatic interaction Arg8 with a negatively charged receptor residue. In order identify such residue, conserved acidic residues the mouse were mutated isosteric Asn or Gln. Mutant receptors tested decreased preference Arg8-containing ligands by ligand and inositol phosphate production. One mutants, in which Glu301 was Gln, exhibited 56-fold decrease apparent GnRH. mutant also [Lys8]GnRH, but its [Gln8]GnRH unchanged compared wild type receptor. analogue, [Glu8]GnRH, increased more than 10-fold. did not, therefore, distinguish analogues amino acid substitutions as effectively loss discrimination specific 8, because favorable positions 5, 6, 7. These findings show that plays role recognition are consistent between these 2 residues.