Proper receptor signalling in a mutant catfish gonadotropin-releasing hormone receptor lacking the highly conserved Asp(90) residue.
The negatively charged side chain of an Asp residue in transmembrane domain 2 is likely to play an important role in receptor signalling since it is highly conserved in the whole family of G protein-coupled receptors, except in mammalian gonadotropin-releasing hormone (GnRH) receptors. In this paper we show that the conserved Asp(90) of the catfish GnRH receptor can be substituted by a neutral Asn(90) without abolishing receptor signalling if another negatively charged Glu(93) is introduced in a proximal region of the receptor interior, thereby mimicking the Glu(90)-Lys(121) salt bridge of mammalian GnRH receptors.
Blomenröhr
M
M
Department of Experimental Zoology, Utrecht University, The Netherlands.
Kühne
R
R
Hund
E
E
Leurs
R
R
Bogerd
J
J
ter Laak
T
T
D000818:Animals; D001224:Aspartic Acid / Q000235:genetics; D001665:Binding Sites; D002397:Catfishes; D017124:Conserved Sequence; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism*; D006801:Humans; D007295:Inositol Phosphates / Q000378:metabolism; D008239:Lysine / Q000235:genetics; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D017434:Protein Structure, Tertiary; D011966:Receptors, LHRH / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
D007295:Inositol Phosphates; D011966:Receptors, LHRH; D001224:Aspartic Acid; D007987:Gonadotropin-Releasing Hormone; D008239:Lysine