fendo-06-00140.pdf 2,81MB
1000 Titel
  • Differences in signal activation by LH and hCG are mediated by the LH/CG receptor’s extracellular hinge region
1000 Autor/in
  1. Grzesik, Paul |
  2. Kreuchwig, Annika |
  3. Rutz, Claudia |
  4. Furkert, Jens |
  5. Wiesner, Burkhard |
  6. Schuelein, Ralf |
  7. Kleinau, Gunnar |
  8. Gromoll, Joerg |
  9. Krause, Gerd |
1000 Erscheinungsjahr 2015
1000 LeibnizOpen
1000 Publikationstyp
  1. Artikel |
1000 Online veröffentlicht
  • 2015-09-22
1000 Erschienen in
1000 Quellenangabe
  • 6: 140
1000 FRL-Sammlung
1000 Copyrightjahr
  • 2015
1000 Lizenz
1000 Verlagsversion
  • |
  • |
1000 Ergänzendes Material
  • |
1000 Publikationsstatus
1000 Begutachtungsstatus
1000 Sprache der Publikation
1000 Abstract/Summary
  • The human lutropin (hLH)/choriogonadotropin (hCG) receptor (LHCGR) can be activated by binding two slightly different gonadotropic glycoprotein hormones, choriogonadotropin (CG) – secreted by the placenta, and lutropin (LH) – produced by the pituitary. They induce different signaling profiles at the LHCGR. This cannot be explained by binding to the receptor’s leucine-rich-repeat domain (LRRD), as this binding is similar for the two hormones. We therefore speculate that there are previously unknown differences in the hormone/receptor interaction at the extracellular hinge region, which might help to understand functional differences between the two hormones. We have therefore performed a detailed study of the binding and action of LH and CG at the LHCGR hinge region. We focused on a primate-specific additional exon in the hinge region, which is located between LRRD and the serpentine domain. The segment of the hinge region encoded by exon10 was previously reported to be only relevant to hLH signaling, as the exon10-deletion receptor exhibits decreased hLH signaling, but unchanged hCG signaling. We designed an advanced homology model of the hormone/LHCGR complex, followed by experimental characterization of relevant fragments in the hinge region. In addition, we examined predictions of a helical exon10-encoded conformation by block-wise polyalanine (helix supporting) mutations. These helix preserving modifications showed no effect on hormone-induced signaling. However, introduction of a structure-disturbing double-proline mutant LHCGR-Q303P/E305P within the exon10-helix has, in contrast to exon10-deletion, no impact on hLH, but only on hCG signaling. This opposite effect on signaling by hLH and hCG can be explained by distinct sites of hormone interaction in the hinge region. In conclusion, our analysis provides details of the differences between hLH- and hCG-induced signaling that are mainly determined in the L2-beta loop of the hormones and in the hinge region of the receptor.
1000 Sacherschließung
lokal GPCR activation
lokal glycoprotein hormone receptors
lokal lutropin receptor
lokal choriogonadotropin
lokal lutropin
1000 Fächerklassifikation (DDC)
1000 Liste der Beteiligten
1000 Label
1000 Förderer
  1. German Research Foundation (DFG) |
1000 Fördernummer
  1. GR 1547/9-1; KR1273/2-1
1000 Förderprogramm
  1. -
1000 Dateien
1000 Förderung
  1. 1000 joinedFunding-child
    1000 Förderer German Research Foundation (DFG) |
    1000 Förderprogramm -
    1000 Fördernummer GR 1547/9-1; KR1273/2-1
1000 Objektart article
1000 Beschrieben durch
1000 @id frl:6404895.rdf
1000 Erstellt am 2017-10-09T17:43:39.676+0200
1000 Erstellt von 218
1000 beschreibt frl:6404895
1000 Bearbeitet von 218
1000 Zuletzt bearbeitet Thu Aug 18 07:51:08 CEST 2022
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1000 Vgl. frl:6404895
1000 Oai Id
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1000 Sichtbarkeit Metadaten public
1000 Sichtbarkeit Daten public
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