PMID- 1715920
OWN - NLM
STAT- MEDLINE
DCOM- 19911004
LR  - 20191028
IS  - 0197-5110 (Print)
IS  - 0197-5110 (Linking)
VI  - 11
IP  - 1-4
DP  - 1991
TI  - Relationship of orientation with affinity and activity of receptor-bound 
      glycosylation variants of human chorionic gonadotropin (hCG), as visualized by 
      monoclonal antibodies (MCA).
PG  - 437-58
AB  - When hCG was receptor-bound, only 2 epitopes (i.e. beta 3 and beta 5) out of its 
      previously mapped total of 14 surface epitopes (10, 11, 12) could be detected by 
      the respective 125I-MCA. Clearly, this indicates a non-random orientation of hCG 
      in this particular state (1). Now we report that on receptor-bound desialylated 
      (asialo-hCG) as well as on receptor-bound deglycosylated hCG (degly-hCG), the 
      beta 3 and beta 5 epitopes were inaccessible for 125I-MCA as were the remaining 
      epitopes, although both variants, when not receptor-bound, were indistinguishable 
      from native hCG with respect to number and topography of epitopes. Thus, the 
      carbohydrate (CHO) units of hCG neither seem to be part of these 14 antigenic 
      sites nor to contribute to the affinity of receptor binding: both variants had 
      even higher affinities than native hCG. However, since the CHO are known to be 
      obligatory for triggering the postreceptor responses of hCG-stimulated target 
      cells, as seen by the 50% reduced or totally abolished biological potency of 
      asialo-hCG and degly-hCG, respectively, the here demonstrated clear-cut 
      differences in epitope accessibility can be related to differences in 
      receptor-bound orientations which reflect signal transduction-competent and 
      incompetent modes of interaction with the receptor. We believe that the CHO, 
      while not contributing to receptor binding per se, function to assure correct 
      positioning of hCG in the ligand recognition domain to allow for proper 
      protein-protein interactions between ligand and receptor and thus optimal 
      activation and hence transduction of the external signal to the cell's interior. 
      In addition, the fact that most of the surface epitopes were masked on 
      receptor-bound hCG, represents the first experimental support for the sofar 
      unproven hypothesis that this unusually long (i.e. 341 amino acid residues) 
      extracellular N' terminal domain of the recently cloned hCG receptor (hCG-R) 
      (23,24), is indeed involved in ligand recognition.
FAU - Schwarz, S
AU  - Schwarz S
AD  - Institute of General & Experimental Pathology, Faculty of Medicine, University of 
      Innsbruck, Austria.
FAU - Krude, H
AU  - Krude H
FAU - Nelboeck, E
AU  - Nelboeck E
FAU - Berger, P
AU  - Berger P
FAU - Merz, W E
AU  - Merz WE
FAU - Wick, G
AU  - Wick G
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Recept Res
JT  - Journal of receptor research
JID - 8008358
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Chorionic Gonadotropin)
RN  - 0 (Epitopes)
RN  - 0 (Receptors, LH)
SB  - IM
MH  - Animals
MH  - Antibodies, Monoclonal
MH  - Chorionic Gonadotropin/*metabolism
MH  - Epitopes/analysis
MH  - Glycosylation
MH  - In Vitro Techniques
MH  - Male
MH  - Radioligand Assay
MH  - Rats
MH  - Rats, Inbred Strains
MH  - Receptors, LH/*metabolism
MH  - Testis/metabolism
EDAT- 1991/01/01 00:00
MHDA- 1991/01/01 00:01
CRDT- 1991/01/01 00:00
PHST- 1991/01/01 00:00 [pubmed]
PHST- 1991/01/01 00:01 [medline]
PHST- 1991/01/01 00:00 [entrez]
AID - 10.3109/10799899109066420 [doi]
PST - ppublish
SO  - J Recept Res. 1991;11(1-4):437-58. doi: 10.3109/10799899109066420.