Citterio_2018_J.Biol.Chem_293_4860

Reference

Title : Relationship between the dimerization of thyroglobulin and its ability to form triiodothyronine - Citterio_2018_J.Biol.Chem_293_4860
Author(s) : Citterio CE , Morishita Y , Dakka N , Veluswamy B , Arvan P
Ref : Journal of Biological Chemistry , 293 :4860 , 2018
Abstract : Thyroglobulin (TG) is the most abundant thyroid gland protein, a dimeric iodoglycoprotein (660 kDa). TG serves as the protein precursor in the synthesis of thyroid hormones tetraiodothyronine (T4) and triiodothyronine (T3). The primary site for T3 synthesis in TG involves an iodotyrosine acceptor at the antepenultimate Tyr residue (at the extreme carboxyl terminus of the protein). The carboxyl-terminal region of TG comprises a cholinesterase-like (ChEL) domain followed by a short unique tail sequence. Despite many studies, the monoiodotyrosine donor residue needed for the coupling reaction to create T3 at this evolutionarily conserved site remains unidentified. In this report, we have utilized a novel, convenient immunoblotting assay to detect T3 formation after protein iodination in vitro, enabling the study of T3 formation in recombinant TG secreted from thyrocytes or heterologous cells. With this assay, we confirm the antepenultimate residue of TG as a major T3-forming site, but also demonstrate that the side chain of this residue intimately interacts with the same residue in the apposed monomer of the TG dimer. T3 formation in TG, or the isolated carboxyl-terminal region, is inhibited by mutation of this antepenultimate residue, but we describe the first substitution mutation that actually increases T3 hormonogenesis by engineering a novel cysteine, 10 residues upstream of the antepenultimate residue, allowing for covalent association of the unique tail sequences, and that helps to bring residues Tyr(2744) from apposed monomers into closer proximity.
ESTHER : Citterio_2018_J.Biol.Chem_293_4860
PubMedSearch : Citterio_2018_J.Biol.Chem_293_4860
PubMedID: 29440273

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Citations formats

Citterio CE, Morishita Y, Dakka N, Veluswamy B, Arvan P (2018)
Relationship between the dimerization of thyroglobulin and its ability to form triiodothyronine
Journal of Biological Chemistry 293 :4860

Citterio CE, Morishita Y, Dakka N, Veluswamy B, Arvan P (2018)
Journal of Biological Chemistry 293 :4860