fendo-08-00086.pdf 4,60MB
1000 Titel
  • Structural–Functional Features of the Thyrotropin Receptor: A Class A G-Protein-Coupled Receptor at Work
1000 Autor/in
  1. Kleinau, Gunnar |
  2. Worth, Catherine L. |
  3. Kreuchwig, Annika |
  4. Biebermann, Heike |
  5. Marcinkowski, Patrick |
  6. Scheerer, Patrick |
  7. Krause, Gerd |
1000 Erscheinungsjahr 2017
1000 LeibnizOpen
1000 Publikationstyp
  1. Artikel |
1000 Online veröffentlicht
  • 2017-04-24
1000 Erschienen in
1000 Quellenangabe
  • 8: 86
1000 FRL-Sammlung
1000 Copyrightjahr
  • 2017
1000 Lizenz
1000 Verlagsversion
  • |
  • |
1000 Publikationsstatus
1000 Begutachtungsstatus
1000 Sprache der Publikation
1000 Abstract/Summary
  • The thyroid-stimulating hormone receptor (TSHR) is a member of the glycoprotein hormone receptors, a sub-group of class A G-protein-coupled receptors (GPCRs). TSHR and its endogenous ligand thyrotropin (TSH) are of essential importance for growth and function of the thyroid gland and proper function of the TSH/TSHR system is pivotal for production and release of thyroid hormones. This receptor is also important with respect to pathophysiology, such as autoimmune (including ophthalmopathy) or non-autoimmune thyroid dysfunctions and cancer development. Pharmacological interventions directly targeting the TSHR should provide benefits to disease treatment compared to currently available therapies of dysfunctions associated with the TSHR or the thyroid gland. Upon TSHR activation, the molecular events conveying conformational changes from the extra- to the intracellular side of the cell across the membrane comprise reception, conversion, and amplification of the signal. These steps are highly dependent on structural features of this receptor and its intermolecular interaction partners, e.g., TSH, antibodies, small molecules, G-proteins, or arrestin. For better understanding of signal transduction, pathogenic mechanisms such as autoantibody action and mutational modifications or for developing new pharmacological strategies, it is essential to combine available structural data with functional information to generate homology models of the entire receptor. Although so far these insights are fragmental, in the past few decades essential contributions have been made to investigate in-depth the involved determinants, such as by structure determination via X-ray crystallography. This review summarizes available knowledge (as of December 2016) concerning the TSHR protein structure, associated functional aspects, and based on these insights we suggest several receptor complex models. Moreover, distinct TSHR properties will be highlighted in comparison to other class A GPCRs to understand the molecular activation mechanisms of this receptor comprehensively. Finally, limitations of current knowledge and lack of information are discussed highlighting the need for intensified efforts toward TSHR structure elucidation.
1000 Fächerklassifikation (DDC)
1000 Liste der Beteiligten
1000 Label
1000 Förderer
  1. Deutsche Forschungsgemeinschaft (DFG) |
  2. DFG Cluster of Excellence |
1000 Fördernummer
  1. KR1273/4-2; BI 893/6-3; SFB740-B6
  2. Research Field D3/E3-1
1000 Förderprogramm
  1. -
  2. “Unifying Concepts in Catalysis"
1000 Dateien
1000 Förderung
  1. 1000 joinedFunding-child
    1000 Förderer Deutsche Forschungsgemeinschaft (DFG) |
    1000 Förderprogramm -
    1000 Fördernummer KR1273/4-2; BI 893/6-3; SFB740-B6
  2. 1000 joinedFunding-child
    1000 Förderer DFG Cluster of Excellence |
    1000 Förderprogramm “Unifying Concepts in Catalysis"
    1000 Fördernummer Research Field D3/E3-1
1000 Objektart article
1000 Beschrieben durch
1000 @id frl:6402732.rdf
1000 Erstellt am 2017-06-02T07:41:30.465+0200
1000 Erstellt von 25
1000 beschreibt frl:6402732
1000 Bearbeitet von 288
1000 Zuletzt bearbeitet Thu Aug 18 08:02:06 CEST 2022
1000 Objekt bearb. Wed Mar 31 07:09:34 CEST 2021
1000 Vgl. frl:6402732
1000 Oai Id
  1. |
1000 Sichtbarkeit Metadaten public
1000 Sichtbarkeit Daten public
1000 Gegenstand von

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