Structural requirements for alpha-mating factor activity.
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.
Houen
G
G
Department of Autoimmunology, Statens Seruminstitut, Copenhagen, Denmark.
Nielsen
O
O
Flanagan
C
C
D000595:Amino Acid Sequence; D000818:Animals; D002064:Buserelin / Q000737:chemistry; D002462:Cell Membrane / Q000378:metabolism; D002645:Chickens; D005399:Fishes; D007987:Gonadotropin-Releasing Hormone / Q000737:chemistry; D008322:Mammals; D013058:Mass Spectrometry; D000072235:Mating Factor; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism* / Q000494:pharmacology; D010675:Pheromones / Q000737:chemistry / Q000378:metabolism; D011966:Receptors, LHRH / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000502:physiology*; D017386:Sequence Homology, Amino Acid
D010455:Peptides; D010675:Pheromones; D011966:Receptors, LHRH; D007987:Gonadotropin-Releasing Hormone; D000072235:Mating Factor; D002064:Buserelin