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Data from: Computational model of the full-length TSH receptor


Mezei, Mihaly; Latif, Rauf; Davies, Terry (2023), Data from: Computational model of the full-length TSH receptor, Dryad, Dataset,


The receptor for thyroid stimulating hormone (TSHR), a GPCR, is of particular interest as the primary antigen in autoimmune hyperthyroidism (Graves' disease) caused by stimulating TSHR antibodies. To date, only one domain of the extracellular region of the TSHR has been crystallized. We have run a 1000ns Molecular Dynamic simulation on a model of the entire TSHR generated by merging the extracellular region of the receptor, obtained using artificial intelligence, with our recent homology model of the transmembrane domain, embedded it in a lipid membrane solvated it with water and counterions. The simulations showed that the structure of the transmembrane and leucine-rich domains were remarkably constant while the linking region (LR), known more commonly as the "hinge region", showed significant flexibility, forming several transient secondary structural elements. Furthermore, the relative orientation of the leucine-rich domain with the rest of the receptor was also seen to be variable. These data suggest that this linker region is an intrinsically disordered protein (IDP). Furthermore, preliminary data simulating the full TSHR model complexed with its ligand (TSH) showed that (a) there is a strong affinity between the linker region and TSH ligand and (b) the association of the linker region and the TSH ligand reduces the structural fluctuations in the linker region. This full-length model illustrates the importance of the linker region in responding to ligand binding and lays the foundation for studies of pathologic TSHR autoantibodies complexed with the TSHR to give further insight into their interaction with the flexible linker region.

The dataset represents the coordinates of a model of the Thyroid Stimulating Hormone Recpetor (TSHR) built from the AI-based alphafold2 model of the TSHR ectodomain and the MD geverated model of the transmembrane domain (TMD) of TSHR.


The cooordinates were generated by judiciously chosen translation and rotation of the ecodomain model to merge it with the TMD model.

Usage notes

The file is in the classic PDB format - any molecular graphics program (e.g., VMD) can display it.


National Institute of Diabetes and Digestive and Kidney Diseases, Award: DK069713 (PI: TF)

U.S. Department of Veterans Affairs, Award: BX000800 (Merit award to TF)