Receptor-selective determinants in catfish gonadotropin seat-belt loops.
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.
Vischer
Henry F
HF
Department of Endocrinology, Utrecht University, 3584 CH Utrecht, The Netherlands.
Marques
Rute B
RB
Granneman
Joke C M
JC
Linskens
Maarten H K
MH
Schulz
Rüdiger W
RW
Bogerd
Jan
J
D000595:Amino Acid Sequence; D000818:Animals; D002397:Catfishes / Q000235:genetics / Q000378:metabolism*; D017124:Conserved Sequence; D003545:Cysteine / Q000235:genetics; D004023:Dictyostelium / Q000235:genetics; D005260:Female; D037201:Follicle Stimulating Hormone, beta Subunit / Q000737:chemistry* / Q000235:genetics / Q000494:pharmacology*; D037101:Luteinizing Hormone, beta Subunit / Q000737:chemistry* / Q000235:genetics / Q000494:pharmacology*; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D011967:Receptors, Gonadotropin / Q000819:agonists / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D016415:Sequence Alignment; D013329:Structure-Activity Relationship; D037322:Thyrotropin, beta Subunit / Q000235:genetics
D037201:Follicle Stimulating Hormone, beta Subunit; D037101:Luteinizing Hormone, beta Subunit; D011967:Receptors, Gonadotropin; D011993:Recombinant Fusion Proteins; D037322:Thyrotropin, beta Subunit; D003545:Cysteine