Receptor-selective determinants in catfish gonadotropin seat-belt loops.

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.

journal_name

Mol Cell Endocrinol

authors

Vischer HF,Marques RB,Granneman JC,Linskens MH,Schulz RW,Bogerd J

doi

10.1016/j.mce.2004.06.011

keywords:

subject

Has Abstract

pub_date

2004-09-30 00:00:00

pages

55-63

issue

1-2

eissn

0303-7207

issn

1872-8057

pii

S0303-7207(04)00276-X

journal_volume

224

pub_type

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