A defined epitope on the human choriogonadotropin alpha-subunit interacts with the second extracellular loop of the transmembrane domain of the lutropin/choriogonadotropin receptor.
The monoclonal antibody, HT13 recognizes human choriogonadotropin (CG) bound to the extracellular domain of its receptor, but not to the full-length receptor. The HT13 epitope is located in the regions of residues 15-17 and 73-75 of the human CG alpha-subunit. Only one synthetic peptide, lutropin (LH)/CG-receptor-(481-497)-peptide (EL2 peptide), which spans the second putative extracellular loop of the LH/CG-receptor endodomain, prevents recognition of human CG by HT13 mAb. EL2 peptide decreases hormone-induced cAMP production, but not high-affinity binding. An anti-EL2 serum also displays the capacity to inhibit human CG-stimulated cAMP production. These results suggest that the second extracellular loop of the receptor is in contact with the HT13 epitope of human CG alpha-subunit and is involved in signal transduction. A relative orientation of the hormone versus the endodomain is proposed.
Unité Récepteurs et Communication Cellulaire, Bâtiment des Biotechnologies, INRA, France.
L
L
Couture
J J
JJ
Remy
H
H
Rabesona
F
F
Troalen
E
E
Pajot-Augy
V
V
Bozon
T
T
Haertle
J M
JM
Bidart
R
R
Salesse
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D016466:CHO Cells; D006224:Cricetinae; D000242:Cyclic AMP / Q000096:biosynthesis; D000939:Epitopes / Q000737:chemistry; D015292:Glycoprotein Hormones, alpha Subunit / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D015394:Molecular Structure; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology / Q000494:pharmacology; D011487:Protein Conformation; D011817:Rabbits; D011974:Receptors, LH / Q000737:chemistry / Q000378:metabolism*; D015398:Signal Transduction
D000939:Epitopes; D015292:Glycoprotein Hormones, alpha Subunit; D010446:Peptide Fragments; D011974:Receptors, LH; D000242:Cyclic AMP