CHARACTERIZATION OF D117A AND H260A MUTATIONS IN THE MELANOCORTIN-1 RECEPTOR

Recent site directed mutagenesis studies on the melanocortin 1 (MC1) r eceptor have indicated the importance of D117 and H260 amino acid resi dues for the binding of alpha-MSH (melanocyte stimulating hormone). He re, we report the testing of 12 cyclic and linear MSH peptides on the D117A and H260A mutant receptors. Moreover, we constructed a double mu tant which displayed a major loss in affinity for [Nle(4), D-Phe(7)]al pha-MSH. Our new data of His(6) and Phe(7) substituted MSH peptides ar e compared with previous results and the hypothesis of putative intera ctions of D117 and H260 with single amino acids in the MSH peptide. Ou r conclusions are that the D117A and the H260A mutations may cause con formational changes in the receptor which can not be linked to any spe cific amino acid in the MSH-peptides. (C) 1997 Elsevier Science Irelan d Ltd.