DIFFERENCES IN STRUCTURE-FUNCTION RELATIONS BETWEEN NONMAMMALIAN AND MAMMALIAN GONADOTROPIN-RELEASING-HORMONE RECEPTORS

Mammalian gonadotropin-releasing hormone receptors (GnRH-Rs) differ fr om other G protein-coupled receptors in lacking the intracellular C-te rminus and in showing an ex:change of two otherwise highly conserved A sp (D) and Asn (N) residues in transmembrane domains (TMD) 2 and 7, re spectively. However, the first GnRH-R characterized from a nonmammalia n vertebrate, the African catfish, does contain an intracellular C-ter minus and has D residues in TMD 2 and 7. The functional relevance of t hese structural features was analysed with (DN321)-N-90, (ND321)-D-90, (NN321)-N-90 and C-terminally truncated mutant catfish GnRH-Rs. An an tiserum raised again:st the recombinant extracellular domain of the wi ld-type catfish GnRH-R detected all mutant receptors at the cell surfa ce of transiently transfected 293T cells. However, only the (DN321)-N- 90 mutant specifically bound GnRHs and activated signal transduction i n response to GnRHs; all other mutants were inactive in both respects. We conclude that the catfish GnRH-R differs from the mammalian GnRH-R s in that both the C-terminal domain and D-90 in TMD 2 are important f or receptor functioning. (C) 1997 Academic Press.