Receptor-selective determinants in catfish gonadotropin seat-belt loops

Henry F Vischer, Rute B Marques, Joke C M Granneman, Maarten H K Linskens, Rüdiger W Schulz, Jan Bogerd

Research output: Contribution to JournalArticleAcademicpeer-review

Abstract

Mammalian gonadotropins are highly selective. Charge differences between the Cys(10-11) sequence of FSHbeta and LHbeta/CGbeta seat-belt loops determine the ability of these hormones to interact with the LH-R. Selective FSH-R binding is mainly dependent on the presence of an FSHbeta-specific sequence between Cys(11-12) of the seat-belt loop. Intriguingly, African catfish LHbeta (cfLHbeta) lacks a positively charged Cys(10-11) region and stimulates both catfish LH-R and FSH-R with comparable potencies. Our studies on the promiscuous behaviour of cfLH using chimeric gonadotropins revealed that the Cys(10-11) region of cfLHbeta contains cfLH-R-selective determinants, whereas the Cys(11-12) region of cfLHbeta confers FSH-R-stimulating activity to cfLH. Hence, the location of receptor-selective determinants appeared to be fairly well conserved throughout evolution, despite the low sequence identity between mammalian and catfish seat-belt loops. Moreover, various structure-function differences between gonadotropins are discussed in the context of the different (female) reproductive strategies between mammalian and non-mammalian species that required the divergence to a more specific LH-R-stimulating activity of one of the gonadotropins in mammals.

Original languageEnglish
Pages (from-to)55-63
Number of pages9
JournalMolecular and Cellular Endocrinology
Volume224
Issue number1-2
DOIs
Publication statusPublished - 30 Sep 2004

Keywords

  • Amino Acid Sequence
  • Animals
  • Catfishes
  • Conserved Sequence
  • Cysteine
  • Dictyostelium
  • Female
  • Follicle Stimulating Hormone, beta Subunit
  • Luteinizing Hormone, beta Subunit
  • Molecular Sequence Data
  • Mutation
  • Receptors, Gonadotropin
  • Recombinant Fusion Proteins
  • Sequence Alignment
  • Structure-Activity Relationship
  • Thyrotropin, beta Subunit
  • Journal Article

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