ArticleThe Journal of biological chemistry2009
The cholinesterase-like domain, essential in thyroglobulin trafficking for thyroid hormone synthesis, is required for protein dimerization.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 52 citations in OpenAlex.
- Article
- Identification of protein precursor for thyroid hormone synthesis in basal chordate ascidian Styela clava.Nature communications · 2026Article
- LINE-1 transposition into murine Thyroglobulin results in congenital thyroid dysplasia.PloS one · 2025Article
- Article
- Structural features of thyroglobulin linked to protein trafficking.Protein science : a publication of the Protein Society · 2023Article
- Identification of Novel Candidate Genes for Familial Thyroid Cancer by Whole Exome Sequencing.International journal of molecular sciences · 2023Article
- The p.Pro2232Leu variant in the ChEL domain of thyroglobulin gene causes intracellular transport disorder and congenital hypothyroidism.Endocrine · 2023Article
- Cryo-EM structure of native human thyroglobulin.Nature communications · 2022Article
- Thyroid hormone synthesis continues despite biallelic thyroglobulin mutation with cell death.JCI insight · 2021Article
- Cell death-associated lipid droplet protein CIDE-A is a noncanonical marker of endoplasmic reticulum stress.JCI insight · 2021Article
- Thyroglobulin Interactome Profiling Defines Altered Proteostasis Topology Associated With Thyroid Dyshormonogenesis.Molecular & cellular proteomics : MCP · 2021Article
- Increased Prevalence of TG and TPO Mutations in Sudanese Children With Congenital Hypothyroidism.The Journal of clinical endocrinology and metabolism · 2020Article
- Novel TG-FGFR1 and TRIM33-NTRK1 transcript fusions in papillary thyroid carcinoma.Genes, chromosomes & cancer · 2019Article
- The role of thyroglobulin in thyroid hormonogenesis.Nature reviews. Endocrinology · 2019Review
- Relationship between the dimerization of thyroglobulin and its ability to form triiodothyronine.The Journal of biological chemistry · 2018Article
- Hot Spots for Protein Partnerships at the Surface of Cholinesterases and Related α/β Hydrolase Fold Proteins or Domains-A Structural Perspective.Molecules (Basel, Switzerland) · 2017Review
- Evolution, immunity and the emergence of brain superautoantigens.F1000Research · 2017Article
- Thyroglobulin From Molecular and Cellular Biology to Clinical Endocrinology.Endocrine reviews · 2016Review
- Modelling of Thyroid Peroxidase Reveals Insights into Its Enzyme Function and Autoantigenicity.PloS one · 2015Article
- Transient covalent interactions of newly synthesized thyroglobulin with oxidoreductases of the endoplasmic reticulum.The Journal of biological chemistry · 2014Article
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Authors and funding
4 authors at 3 institutions in 3 countries.
Funding
Abstract
The carboxyl-terminal cholinesterase-like (ChEL) domain of thyroglobulin (Tg) has been identified as critically important in Tg export from the endoplasmic reticulum. In a number of human kindreds suffering from congenital hypothyroidism, and in the cog congenital goiter mouse and rdw rat dwarf models, thyroid hormone synthesis is inhibited because of mutations in the ChEL domain that block protein export from the endoplasmic reticulum. We hypothesize that Tg forms homodimers through noncovalent interactions involving two predicted alpha-helices in each ChEL domain that are homologous to the dimerization helices of acetylcholinesterase. This has been explored through selective epitope tagging of dimerization partners and by inserting an extra, unpaired Cys residue to create an opportunity for intermolecular disulfide pairing. We show that the ChEL domain is necessary and sufficient for Tg dimerization; specifically, the isolated ChEL domain can dimerize with full-length Tg or with itself. Insertion of an N-linked glycan into the putative upstream dimerization helix inhibits homodimerization of the isolated ChEL domain. However, interestingly, co-expression of upstream Tg domains, either in cis or in trans, overrides the dimerization defect of such a mutant. Thus, although the ChEL domain provides a nidus for Tg dimerization, interactions of upstream Tg regions with the ChEL domain actively stabilizes the Tg dimer complex for intracellular transport.
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Registered trials
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