Structural requirements for α‐mating factor activity

Structural requirements for α‐mating factor activity
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α交配因子活性的结构要求

DOI:
10.1016/0014-5793(96)00726-0
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发表时间:
1996
期刊:
影响因子:
3.5
通讯作者:
C. Flanagan
C. Flanagan
中科院分区:
生物学3区
文献类型:
--
作者:
G. Houen;O. Nielsen;C. Flanagan

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酿酒酵母的性激素α-交配因子(α-MF,WHWLQLKPGQPMY)与哺乳动物黄体生成素释放激素(LHRH,pEHWSYGLRPG-NH2)具有结构同源性,并且已被证明具有LHRH活性[Loumaye等人,2017]。 (1982) 科学 218, 1323–1325]。我们测试了LHRH在酵母中是否具有α-MF活性,发现没有。因此,我们合成了一系列α-MF和LHRH的杂合肽,以研究决定α-MF和LHRH活性的结构特征。由 LHRH 序列与 α-MF C 端四肽 (QPMY) 组成的杂合肽不表现出 α-MF 活性。因此,LHRH 缺乏 α-MF 活性并不仅仅是由于 C 端残基的缺失。如在 LHRH 中发现的那样,将 α-MF 中的 Lys7 替换为 Arg 并不影响 α-MF 活性,另外用 pGlu 替换 Trp1 也不会影响 α-MF 活性。然而,α-MF 的 C 端四个氨基酸对于 α-MF 活性是必需的。我们的结果表明,在 LHRH 中发现的第 4 位插入 Ser 残基会消除 α-MF 活性。这些结果表明,除了完整的 C 末端之外,N 末端 His2 和 C 末端的正确间距也是 α-MF 活性所必需的。杂合肽均表现出比 LHRH 或 α-MF 更低的 LHRH 活性。这些结构功能研究表明,这两种生殖激素之间的结构同源性可能无法反映它们之间的进化关系。
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 Lys7in α-MF with Arg, as is found in LHRH, did not affect the α-MF activity, nor did an additional substitution of Trp1with 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 His2and 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.
实验性胰腺癌中存在 [D-TRP6]-黄体生成素释放激素的膜结合位点。
DOI: 10.1016/0304-3835(89)90141-9
发表时间: 1989
期刊: Cancer letters
影响因子: 9.7
作者:
Fekete,M;Zalatnai,A;Schally,AV
通讯作者: Schally,AV
通过异源和自体受体刺激的酪氨酸磷酸化调节黄体生成素释放激素受体的结合。
DOI: 10.1073/pnas.88.6.2244
发表时间: 1991
影响因子: 11.1
作者:
Liebow,C;Lee,MT;Kamer,AR;Schally,AV
通讯作者: Schally,AV