Twelve of fourteen surface epitopes of receptor-bound human chorionic gonadotropin (hCG) being antibody-inaccessible suggest an extensive involvement of the long extracellular domain of the hCG receptor.
On the surface of the free (receptor-unbound) form of hCG, we have previously identified 14 topographically distinct epitopes (Schwarz et al. (1986) Endocrinology 118, 189-197; Berger et al. (1990) J. Endocrinol. 125, 301-309). Here we report that only two of them, i.e. the (adjacent) beta 3 and beta 5 epitopes, can be recognized by 125iodine-labeled monoclonal antibodies when hCG was specifically bound to the rat testis hCG receptor. The exclusive accessibility of precisely these two surface epitopes indicates that hCG assumes a defined rather than a stochastic orientation in its receptor-bound state. The inaccessibility of 12 of 14 epitopes is consistent with the idea that the 341 residues long extracellular domain of the recently cloned hCG receptor (MacFarland et al. (1989) Science 245, 494-499) is the ligand binding domain. It is proposed that the extracellular domain is folded in a way that a cavity is formed large enough to accommodate hCG. Thereby, a considerable portion of the total surface of hCG is covered, as reflected by the masking of most of its epitopes.
Schwarz
S
S
Institute of General and Experimental Pathology, School of Medicine, University of Innsbruck, Austria.
Krude
H
H
Wick
G
G
Berger
P
P
D000818:Animals; D000911:Antibodies, Monoclonal; D000954:Antigens, Surface / Q000276:immunology / Q000378:metabolism; D001666:Binding Sites, Antibody; D006063:Chorionic Gonadotropin / Q000378:metabolism*; D000939:Epitopes / Q000276:immunology / Q000378:metabolism; D008297:Male; D008566:Membranes / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D051381:Rats; D011919:Rats, Inbred Strains; D011974:Receptors, LH / Q000276:immunology / Q000378:metabolism*; D013737:Testis / Q000378:metabolism
D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D006063:Chorionic Gonadotropin; D000939:Epitopes; D011974:Receptors, LH