PT  - JOURNAL ARTICLE
AU  - Frank M. Dautzenberg
AU  - Jacqueline Higelin
AU  - Olaf Brauns
AU  - Brigitte Butscha
AU  - Richard L. Hauger
TI  - Five Amino Acids of the <em>Xenopus laevis</em> CRF (Corticotropin-Releasing Factor) Type 2 Receptor Mediate Differential Binding of CRF Ligands in Comparison with Its Human Counterpart
AID  - 10.1124/mol.61.5.1132
DP  - 2002 May 01
TA  - Molecular Pharmacology
PG  - 1132--1139
VI  - 61
IP  - 5
4099  - http://molpharm.aspetjournals.org/content/61/5/1132.short
4100  - http://molpharm.aspetjournals.org/content/61/5/1132.full
SO  - Mol Pharmacol2002 May 01; 61
AB  - The ligand selectivity of human (hCRF2A) and Xenopus laevis (xCRF2) forms of the corticotropin-releasing factor type 2 (CRF2) receptor differs. The purpose of this study was to identify amino acids in these two CRF2receptors conferring these differences. An amino acid triplet in the third extracellular domain (Asp262Leu263Val264 in hCRF2A or Lys264Tyr265Ile266 in xCRF2) was found to diverge between both receptors. When binding and signaling characteristics of receptor mutants hR2KYI and xR2DLV were assessed, the tri-amino acid motif replacement produced receptors with binding properties resembling the xCRF2receptor. The converse mutation created a mutant receptor with a binding pharmacology identical to the profile of the hCRF2Areceptor. This effect was most notable for xR2DLV, which possessed a binding affinity for astressin ∼15-fold greater for astressin than sauvagine. In contrast, the binding profiles of the hCRF2Areceptor and hR2KYI did not differ. These data indicate that another domain of the xCRF2 receptor mediated low-affinity binding of astressin. Two amino acids in the first extracellular domain differ in xCRF2 (Asp69Ser70) and hCRF2A (Glu66Tyr67) receptors. The hCRF2A receptor mutant (hR2DS-KYI) bound astressin with a low affinity indistinguishable from the xCRF2 receptor. Therefore, these data demonstrate that ligand selectivity differences between amphibian and human forms of the CRF2A receptor are governed by these two motifs of the extracellular domains of the xCRF2 receptor.