Structural requirements for α‐mating factor activity

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Abstract
The sexual hormone of S. cerevisiae, α-mating factor (α-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 α-MF activity in yeast and found that it does not. We therefore synthesized a series of hybrid peptides of α-MF and LHRH to study the structural features which determine α-MF and LHRH activities. A hybrid peptide consisting of the LHRH sequence with the C-terminal tetrapeptide (QPMY) of α-MF did not exhibit α-MF activity. Thus, the lack of α-MF activity of LHRH is not due solely to the absence of the C-terminal residues. Substitution of Lys7 in α-MF with Arg, as is found in LHRH, did not affect the α-MF activity, nor did an additional substitution of Trp1 with pGlu. However, the C-terminal four amino acids of α-MF were necessary for α-MF activity. Our results indicate that insertion of a Ser residue in position 4 as found in LHRH abolishes α-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 α-MF activity. The hybrid peptides all exhibited less LHRH activity than either LHRH or α-MF. These structure-function studies indicate that the structural homology between these two reproductive hormones may not reflect an evolutionary relationship between them.