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Thyroid hormone receptor

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Structure of human thyroid hormone receptor ligand-binding domain complex with thyroid hormone and cacodylate (PDB entry 1xzx)

Drag the structure with the mouse to rotate

1 Function
2 Disease
3 Relevance
4 Structural highlights
5 3D Structures of thyroid hormone receptor
6 References

Function

Thyroid hormone receptors (TR) are expressed as 2 proteins: TRα and TRβ. TR is a ligand-dependent transcription factor that mediates the biological activity of the thyroid hormone (triiodo-thyronine). TR contains DNA-binding domain at the center and ligand-binding domain at the C-terminal.

Thyroid hormone receptor alpha1 is involved in brain functions. Its deletion is leading to severe anxiety and morphological changes in the hippocampus^[1].
Thyroid hormone receptor beta1 has a role as inhibitor of tutor progression and metastasis suppressor^[2].

Disease

TRβ-deficient mice exhibit a deficit in auditory function^[3]. Mutations in TRβ cause thyroid hormone resistance syndrome. Mutations in the TRα ar involved in dwarfism^[4]. Loss of normal functions of TR by deletion or mutations could contribute to cancer development^[5].

Relevance

Triiodothyroacetic acid (Triac) is used to suppress thyroid hormone resistance^[6].

Structural highlights

The ^[7].

3D Structures of thyroid hormone receptor

Thyroid hormone receptor 3D structures

References

↑ Bernal J. Thyroid hormone receptors in brain development and function. Nat Clin Pract Endocrinol Metab. 2007 Mar;3(3):249-59. PMID:17315033 doi:10.1038/ncpendmet0424
↑ Martínez-Iglesias O, Garcia-Silva S, Tenbaum SP, Regadera J, Larcher F, Paramio JM, Vennström B, Aranda A. Thyroid hormone receptor beta1 acts as a potent suppressor of tumor invasiveness and metastasis. Cancer Res. 2009 Jan 15;69(2):501-9. PMID:19147563 doi:10.1158/0008-5472.CAN-08-2198
↑ Forrest D, Erway LC, Ng L, Altschuler R, Curran T. Thyroid hormone receptor beta is essential for development of auditory function. Nat Genet. 1996 Jul;13(3):354-7. doi: 10.1038/ng0796-354. PMID:8673137 doi:http://dx.doi.org/10.1038/ng0796-354
↑ Cheng SY. Thyroid hormone receptor mutations and disease: beyond thyroid hormone resistance. Trends Endocrinol Metab. 2005 May-Jun;16(4):176-82. doi:, 10.1016/j.tem.2005.03.008. PMID:15860414 doi:http://dx.doi.org/10.1016/j.tem.2005.03.008
↑ Kim WG, Cheng SY. Thyroid hormone receptors and cancer. Biochim Biophys Acta. 2013 Jul;1830(7):3928-36. doi:, 10.1016/j.bbagen.2012.04.002. Epub 2012 Apr 6. PMID:22507269 doi:http://dx.doi.org/10.1016/j.bbagen.2012.04.002
↑ Kunitake JM, Hartman N, Henson LC, Lieberman J, Williams DE, Wong M, Hershman JM. 3,5,3'-triiodothyroacetic acid therapy for thyroid hormone resistance. J Clin Endocrinol Metab. 1989 Aug;69(2):461-6. doi: 10.1210/jcem-69-2-461. PMID:2753985 doi:http://dx.doi.org/10.1210/jcem-69-2-461
↑ Sandler B, Webb P, Apriletti JW, Huber BR, Togashi M, Cunha Lima ST, Juric S, Nilsson S, Wagner R, Fletterick RJ, Baxter JD. Thyroxine-thyroid hormone receptor interactions. J Biol Chem. 2004 Dec 31;279(53):55801-8. Epub 2004 Oct 4. PMID:15466465 doi:10.1074/jbc.M410124200