Differences in structure-function relations between nonmammalian and mammalian gonadotropin-releasing hormone receptors.
Mammalian gonadotropin-releasing hormone receptors (GnRH-Rs) differ from other G protein-coupled receptors in lacking the intracellular C-terminus and in showing an exchange of two otherwise highly conserved Asp (D) and Asn (N) residues in transmembrane domains (TMD) 2 and 7, respectively. However, the first GnRH-R characterized from a nonmammalian vertebrate, the African catfish, does contain an intracellular C-terminus and has D residues in TMD 2 and 7. The functional relevance of these structural features was analysed with D90N321, N90D321, N90N321 and C-terminally truncated mutant catfish GnRH-Rs. An antiserum raised against the recombinant extracellular domain of the wild-type catfish GnRH-R detected all mutant receptors at the cell surface of transiently transfected 293T cells. However, only the D90N321 mutant specifically bound GnRHs and activated signal transduction in response to GnRHs; all other mutants were inactive in both respects. We conclude that the catfish GnRH-R differs from the mammalian GnRH-Rs in that both the C-terminal domain and D90 in TMD 2 are important for receptor functioning.
Blomenröhr
M
M
Research Group for Comparative Endocrinology, University of Utrecht, Utrecht, The Netherlands. m.blomenrohr@biol.ruu.nl
Bogerd
J
J
Leurs
R
R
Schulz
R W
RW
Tensen
C P
CP
Zandbergen
M A
MA
Goos
H J
HJ
D000595:Amino Acid Sequence; D000818:Animals; D005399:Fishes; D006801:Humans; D008322:Mammals; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D011966:Receptors, LHRH / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D017421:Sequence Analysis; D013045:Species Specificity; D013329:Structure-Activity Relationship
D011966:Receptors, LHRH