Thyroid Stimulating Hormone Receptor (TSHR) Structure and Function
Introduction
In humans, the hypothalamic-pituitary-thyroid (HPT) signaling axis regulates functions including metabolism, growth, organ development, and neural differentiation [1]. In this pathway, the thyroid stimulating hormone receptor (TSHR) activates transcription of thyroid hormones in response to ligand binding by thyroid stimulating hormone (TSH). After a brief introduction to the biological significance of TSHR, this page explores the structure of TSHR and its significance to TSH binding and receptor activation.
Biological Significance of TSHR
The HPT signaling axis involves the brain, thyroid gland, and bloodstream circulation. In the first step of the pathway, thyrotropin releasing hormone (TRH) is secreted by the hypothalamus, which in turn stimulates the anterior pituitary gland to produce TSH [1]. TSH binds to TSHR on the surface of thyroid cells and triggers the production of thyroid hormones thyroxine (T3) and triiodothyronine (T4) through G-protein coupled receptor (GPCR) signaling [2]. T3 and T4 are released into the bloodstream circulation and help to regulate metabolism, including through negative feedback loop inhibition of further TSH production [1].
The Malfunction of TSHR, or its TSH ligand, can lead to disease. In Grave's disease, production of a
Structural Overview of TSHR
Describe the domains here.
TSHR Activation
Hinge Motion
Describe the hinge motion and biological function here.
This shows the TSHR hinge movement.
This shows the TSHR hinge movement.
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- Image:TSHR MorphBetterAngle.mp4
Stabilizing Interactions in the Hinge
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Ligand Binding
Ligand-induced Conformation Change
Describe how TSH binds in the upright conformation here.
Ligand Recognition
Describe seatbelt and hinge important to ligand recognition here.
References
- ↑ 1.0 1.1 1.2 Brent GA. Mechanisms of thyroid hormone action. J Clin Invest. 2012;122(9):3035-3043. DOI: 10.1172/JCI60047
- ↑ Chu YD, Yeh CT. The Molecular Function and Clinical Role of Thyroid Stimulating Hormone Receptor in Cancer Cells. Cells. 2020;9(7):1730. DOI:10.3390/cells9071730
