Characterisation of D117A and H260A mutations in the melanocortin 1 receptor

[摘要] Recent site directed mutagenesis studies on the melanocortin 1 (MC1) receptor have indicated the importance of D117 and H260 amino acid residues for the binding of alpha-MSH (melanocyte stimulating hormone). Here, we report the testing of 12 cyclic and linear MSH peptides on the D117A and H260A mutant receptors. Moreover, we constructed a double mutant which displayed a major loss in affinity for [Nle(4), D-Phe(7)]alpha-MSH. Our new data of His(6) and Phe(7) substituted MSH peptides are compared with previous results and the hypothesis of putative interactions of D117 and H260 with single amino acids in the MSH peptide. Our conclusions are that the D117A and the H260A mutations may cause conformational changes in the receptor which can not be linked to any specific amino acid in the MSH-peptides. (C) 1997 Elsevier Science Ireland Ltd.

[发布日期] 1997-02-07

[关键词] MC1 receptor;MSH;ligand binding;mutagenesis