Hormone interactions to Leu-rich repeats in the gonadotropin receptors. II. Analysis of Leu-rich repeat 4 of human luteinizing hormone/chorionic gonadotropin receptor.
The luteinizing hormone receptor (LHR) consists of an approximately 350-amino acid-long N-terminal extracellular exodomain and a membrane-associated endodomain of similar size. Human chorionic gonadotropin (hCG) binds to the exodomain, and then hCG/exodomain complex is thought to make a secondary contact with the endodomain and generate hormone signals. The sequence alignment of the exodomain shows imperfectly matching eight to nine Leu-rich repeats (LRRs). In the preceding article (Song, Y., Ji, I., Beauchamp, J., Isaacs, N., and Ji, T. (2001) J. Biol. Chem. 276, 3426-3435), we have shown that LRR2 and LRR4 are crucial for hormone binding. In this work, we have examined the residues of LRR4, in particular Leu(103) and Ile(105) in the putative beta strand. Our data show that Leu(103) and Ile(105) are involved in the specific, hydrophobic interaction of the LRR4 loop, likely to form the hydrophobic core. This loop is crucial for the structural integrity of all of the LRRs. In contrast, the downstream sequence consisting of Asn(107), Thr(108), Gly(109), and Ile(110) of LRR4 is crucial for cAMP induction but not for hormone binding, folding, and surface expression. This implicates, for the first time, its involvement in the interaction with the endodomain and signal generation. The evidence for the interaction is presented in the following article.
Song
Y S
YS
Department of Chemistry, University of Kentucky, Lexington, Kentucky 40506-0055, USA.
Ji
I
I
Beauchamp
J
J
Isaacs
N W
NW
Ji
T H
TH
D020816:Amino Acid Motifs; D019943:Amino Acid Substitution; D002478:Cells, Cultured; D006063:Chorionic Gonadotropin / Q000378:metabolism*; D006801:Humans; D007532:Isoleucine / Q000235:genetics; D007930:Leucine / Q000235:genetics; D000090263:Leucine-Rich Repeat Proteins; D008958:Models, Molecular; D009154:Mutation; D011506:Proteins / Q000737:chemistry / Q000378:metabolism*; D011974:Receptors, LH / Q000737:chemistry / Q000378:metabolism*
D006063:Chorionic Gonadotropin; D000090263:Leucine-Rich Repeat Proteins; D011506:Proteins; D011974:Receptors, LH; D007532:Isoleucine; D007930:Leucine