This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager NURSA Molecule Pages Link Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Sagar, G. D. V. Articles by Bianco, A. C. Search for Related Content PubMed PubMed Citation Articles by Sagar, G. D. V. Articles by Bianco, A. C.

The Thyroid Hormone-Inactivating Deiodinase Functions as a Homodimer

Thyroid Section (G.D.V.S., C.C.-M., J.W.H., C.L., P.R.L., A.C.B.), Division of Endocrinology, Diabetes and Hypertension, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts 02115; Laboratory of Endocrine Neurobiology (B.G., A.Z.), Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest H-1083 Hungary; Department of Structural Biology (I.C., J.-P.M.), Institut de Minéralogie et de Physique des Milieux Condensés, Centre National de la Recherche Scientifique Unité Mixte de Recherche 7590, Universities Paris 6 and Paris 7, Paris, France; and Division of Endocrinology (M.A.M., S.A.H.), Children’s Hospital Boston, Harvard Medical School Boston, Massachusetts 02115

Address all correspondence and requests for reprints to: Antonio C. Bianco, M.D., Ph.D., Thyroid Section, Brigham and Women’s Hospital, 77 Avenue Louis Pasteur, Harvard Institutes of Medicine Building, Suite 643, Boston, Massachusetts 02115. E-mail: abianco{at}deiodinase.org.

The type 3 deiodinase (D3) inactivates thyroid hormone action by catalyzing tissue-specific inner ring deiodination, predominantly during embryonic development. D3 has gained much attention as a player in the euthyroid sick syndrome, given its robust reactivation during injury and/or illness. Whereas much of the structure biology of the deiodinases is derived from studies with D2, a dimeric endoplasmic reticulum obligatory activating deiodinase, little is known about the holostructure of the plasma membrane resident D3, the deiodinase capable of thyroid hormone inactivation. Here we used fluorescence resonance energy transfer in live cells to demonstrate that D3 exists as homodimer. While D3 homodimerized in its native state, minor heterodimerization was also observed between D3:D1 and D3:D2 in intact cells, the significance of which remains elusive. Incubation with 0.5–1.2 M urea resulted in loss of D3 homodimerization as assessed by bioluminescence resonance energy transfer and a proportional loss of enzyme activity, to a maximum of approximately 50%. Protein modeling using a D2-based scaffold identified potential dimerization surfaces in the transmembrane and globular domains. Truncation of the transmembrane domain (D3) abrogated dimerization and deiodinase activity except when coexpressed with full-length catalytically inactive deiodinase, thus assembled as D3:D3 dimer; thus the D3 globular domain also exhibits dimerization surfaces. In conclusion, the inactivating deiodinase D3 exists as homo- or heterodimer in living intact cells, a feature that is critical for their catalytic activities.

NURSA Molecule Pages Link:

Ligands:   Thyroid hormone

This article has been cited by other articles:

				G. Aerts, R. Arrojo e Drigo, S. L. J. Van Herck, E. Sammels, D. Mirebeau-Prunier, B. Gereben, A. Zeold, J. W. Harney, S. A. Huang, M. A. Mulcahey, et al. Knockdown of the Type 3 Iodothyronine Deiodinase (D3) Interacting Protein Peroxiredoxin 3 Decreases D3-Mediated Deiodination in Intact Cells Endocrinology, November 1, 2009; 150(11): 5171 - 5180. [Abstract] [Full Text] [PDF]

				B. Gereben, A. M. Zavacki, S. Ribich, B. W. Kim, S. A. Huang, W. S. Simonides, A. Zeold, and A. C. Bianco Cellular and Molecular Basis of Deiodinase-Regulated Thyroid Hormone Signaling Endocr. Rev., December 1, 2008; 29(7): 898 - 938. [Abstract] [Full Text] [PDF]