Hormone interactions to Leu-rich repeats in the gonadotropin receptors. III. Photoaffinity labeling of human chorionic gonadotropin with receptor Leu-rich repeat 4 peptide.
Human chorionic gonadotropin (hCG) binds to the extracellular N-terminal domain, exodomain, of its receptor, and the resulting hCG-exodomain complex is thought to modulate the membrane associated domain, endodomain, of the receptor to generate hormone signal. The bulk of the exodomain is speculated to assume a crescent structure consisting of eight to nine Leu-rich repeats (LRRs), which may provide the hormone contact sites. Unfortunately, little experimental evidence is available for the precise hormone contact points in the exodomain and the endodomain. The two preceding articles (Song, Y., Ji, I., Beauchamp, J., Isaacs, N., and Ji, T. (2001) J. Biol. Chem. 276, 3426-3435; Song, Y., Ji, I., Beauchamp, J., Isaacs, N., and Ji, T. (2001) J. Biol. Chem. 276, 3436-3442) show that putative LRR2 and LRR4 are crucial for hormone binding. In particular, the N-terminal region of LRR4 assumes the hydrophobic core of the LRR4 loop, whereas the C-terminal region is crucial for signal generation. However, it is unclear whether LRR4 interacts hCG and the endodomain and how it might be involved in signal generation. In this article, our affinity labeling results present the first evidence that the N-terminal region of LRR4 interacts with hCG, preferentially the hCGalpha subunit and that the hCG/LRR4 complex interacts with exoloop 2 of the endodomain. This interaction offers a mechanism to generate hormone signal.
Jeoung
M
M
Department of Chemistry, University of Kentucky, Lexington, Kentucky 40506-0055, USA.
Phang
T
T
Song
Y S
YS
Ji
I
I
Ji
T H
TH
D020816:Amino Acid Motifs; D019943:Amino Acid Substitution; D001665:Binding Sites; D002478:Cells, Cultured; D006063:Chorionic Gonadotropin / Q000378:metabolism*; D006801:Humans; D007457:Iodine Radioisotopes; D000090263:Leucine-Rich Repeat Proteins; D008958:Models, Molecular; D019920:Photoaffinity Labels / Q000378:metabolism*; D011506:Proteins / Q000737:chemistry / Q000378:metabolism*; D011974:Receptors, LH / Q000737:chemistry / Q000378:metabolism*
D006063:Chorionic Gonadotropin; D007457:Iodine Radioisotopes; D000090263:Leucine-Rich Repeat Proteins; D019920:Photoaffinity Labels; D011506:Proteins; D011974:Receptors, LH