Extended and Structurally Supported Insights into Extracellular Hormone Binding, Signal Transduction and Organization of the Thyrotropin Receptor

• DOI: 10.1371/journal.pone.0052920
• Publication Date: 2012-12-27T23:33:23Z
• Authors: Gerd Krause; Annika Kreuchwig; Gunnar Kleinau
• Keywords: Thyrotropin receptor; Leucine-rich repeat; Thyrotropin-releasing hormone receptor

The hormone thyrotropin (TSH) and its receptor (TSHR) are crucial for the growth function of thyroid gland. TSHR is evolutionary linked with receptors follitropin (FSHR) lutropin/choriogonadotropin (LHR) their sequences structures similar. extracellular region contains more than 350 amino acids binds antibodies. Several important questions related to functions mechanisms still not comprehensively understood. One major reason these open lack any structural information about segment that connects N-terminal leucine-rich repeat domain (LRRD) transmembrane helix (TMH) 1, hinge region. It has been shown experimentally this fine tuning signaling ligand interactions. A new crystal structure containing most hFSHR in complex hFSH recently published. Now, we have applied insights homologous generated a model LRRD/hinge-region/TSH complex. This combined evaluated experimental data including binding (bTSH, hTSH, thyrostimulin), super-agonistic effects, antibody interactions regulation. These studies consideration significant non-significant led description at TSHR, ligand-induced displacements specific fragments. event triggers conformational changes convergent center LRRD region, activating an “intramolecular agonistic unit” close domain.