Title: | Structural requirements for alpha-mating factor activity |
Author(s): | Houen G; Nielsen O; Flanagan C; |
Address: | "Department of Autoimmunology, Statens Seruminstitut, Copenhagen, Denmark" |
DOI: | 10.1016/0014-5793(96)00726-0 |
ISSN/ISBN: | 0014-5793 (Print) 0014-5793 (Linking) |
Abstract: | "The sexual hormone of S. cerevisiae, alpha-mating factor (alpha-MF, WHWLQLKPGQPMY) has structural homology with mammalian luteinizing hormone releasing hormone (LHRH, pEHWSYGLRPG-NH2) and has been shown to exhibit LHRH activity [Loumaye et al. (1982) Science 218, 1323-1325]. We have tested whether LHRH has alpha-MF activity in yeast and found that it does not. We therefore synthesized a series of hybrid peptides of alpha-MF and LHRH to study the structural features which determine alpha-MF and LHRH activities. A hybrid peptide consisting of the LHRH sequence with the C-terminal tetrapeptide (QPMY) of alpha-MF did not exhibit alpha-MF activity. Thus, the lack of alpha-MF activity of LHRH is not due solely to the absence of the C-terminal residues. Substitution of Lys7 in alpha-MF with Arg, as is found in LHRH, did not affect the alpha-MF activity, nor did an additional substitution of Trp1 with pGlu. However, the C-terminal four amino acids of alpha-MF were necessary for alpha-MF activity. Our results indicate that insertion of a Ser residue in position 4 as found in LHRH abolishes alpha-MF activity. These results suggest that, in addition to an intact C-terminus, correct spacing of the N-terminal His2 and the C-terminus is required for alpha-MF activity. The hybrid peptides all exhibited less LHRH activity than either LHRH or alpha-MF. These structure-function studies indicate that the structural homology between these two reproductive hormones may not reflect an evolutionary relationship between them" |
Keywords: | Amino Acid Sequence Animals Buserelin/chemistry Cell Membrane/metabolism Chickens Fishes Gonadotropin-Releasing Hormone/chemistry Mammals Mass Spectrometry Mating Factor Molecular Sequence Data Peptides/chemical synthesis/*chemistry/*metabolism/pharmacolo; |
Notes: | "MedlineHouen, G Nielsen, O Flanagan, C eng Comparative Study England 1996/08/05 FEBS Lett. 1996 Aug 5; 391(1-2):162-6. doi: 10.1016/0014-5793(96)00726-0" |