Consensus Sequences for Early Iodination and Hormonogenesis in Human Thyroglobulin
Open accessAbstract
Thyroglobulin from a human goiter, containing four atoms of iodine/molecule (660,000 daltons), was iodinated with Na 125I and KI in vitro to achieve a net addition of either 2 or 7.8 atoms of iodine/molecule. After fractionation by high performance liquid chromatography, iodinated tryptic peptides from S-cyanoethylated 125I-thyroglobulin were purified, sequenced, characterized by [125I]iodoamino acid distribution, and localized within thyroglobulins primary structure based upon the published cDNA sequence, (Malthiery, Y., and Lissitsky, S. (1987) Eur. J. Biochem. 165, 491-498). The addition of 2 atoms of iodine/molecule of thyroglobulin produced iodotyrosyls at five principal sites, with no 125I-hormone formation. The addition of 7.8 atoms iodinated the same sites more heavily, produced iodotyrosyls at 10 additional sites, and formed iodothyronines at 5 sites. After addition of 2 atoms of iodine, tyrosyl 24 and 11% of thyroglobulins 125I, while tyrosyl 2572 had 24%, but with 7.8 added atoms of iodine, tyrosyl 24 had more of the thyroglobulins [125I]iodothyronine (36 versus 26%). Since tyrosyls 149, 866, and 1466 were iodinated early but did not form the inner rings of iodothyronines, they are attractive candidates for donors of outer iodothyronyl rings. The sequences around the iodotyrosyls fall into three consensus groups, as follows: 1) Glu/Asp-Tyr, associated with synthesis of thyroxine (residues 24, 2572, and 1309), or iodotyrosine (residues 2586 and 991); 2) Ser/Thr-Tyr-…
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Inspection of the structure within a 15 Å radius of the reported acceptor tyrosines (Sites A-D) identified putative donor tyrosines.
“We inspected our structure within a 15 Å radius of the reported acceptor tyrosines (designated Sites A-D)21 and identified putative donor tyrosines (Figure 2a).”
From The structure of human thyroglobulin (2020) · cites this paper as [21]
When all acceptors (Y24, Y2573, Y2766 and Y1310) were mutated, no T4 synthesis was observed, demonstrating that there are no more than four significant hormonogenic sites in TG.
“As shown in Figure 2c, when we mutated all acceptors (Y24, Y2573, Y2766 and Y1310)21,13 we observed no T4 synthesis, demonstrating that there are no more than four significant hormonogenic sites in TG.”
From The structure of human thyroglobulin (2020) · cites this paper as [21]
Mutating four exposed tyrosines (4eY), suggested as being important for hormonogenesis, gave the same activity as for un-mutated rTG.
“We also mutated four exposed tyrosines (4eY), suggested as being important for hormonogenesis21,24 and obtained the same activity as for un-mutated rTG.”
From The structure of human thyroglobulin (2020) · cites this paper as [21]
A conserved lysine is found in proximity of the donor, and a conserved acidic residue (Glu or Asp) always precedes the acceptor.
“A conserved lysine is found in proximity of the donor, and a conserved acidic residue (Glu or Asp) always precedes the acceptor 21.”
From The structure of human thyroglobulin (2020) · cites this paper as [21]
In the context of the thyroid gland and the iodine cycle in vertebrates, TG's structure effectively combines hormonogenesis with iodination of many other solvent exposed tyrosine residues for iodine storage.
“However, in the context of the thyroid gland and the iodine cycle in vertebrates, TG's structure effectively combines hormonogenesis with iodination of many other solvent exposed tyrosine residues for iodine storage21,13.”
From The structure of human thyroglobulin (2020) · cites this paper as [21]
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- Authors
- Lamas, L., Anderson, P. C., Fox, J. W., & Dunn, J. T.
- Affiliations
- University of Virginia (US)
- ORCID
- Fox, J W
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1989-08
- Volume
- 264
- Issue
- 23
- Pages
- 13541-13545
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W1544219463
- Cited by
- 112
- References
- 0
- Citations by year
- 2026: 3 · 2025: 1 · 2024: 3 · 2023: 2 · 2022: 4 · 2021: 6 · 2020: 3 · 2019: 5 · 2018: 2 · 2017: 2 · 2016: 3 · 2015: 1 · 2014: 2 · 2013: 2 · 2012: 1
- FWCI
- 3.12
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Cancer Institute (CA-44579)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK 11043, DK 38942)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Cancer Diagnosis and Treatment
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
- Keywords
- thyroglobulin, iodination, iodothyronines, thyroxine, iodotyrosines, consensus sequence, tyrosine residues, goiter, tryptic peptides, thyroid hormone synthesis
- MeSH terms
- Amino Acid Sequence, Amino Acids, Goiter, Humans, Iodides, Iodine Radioisotopes, Molecular Sequence Data, Peptide Fragments, Thyroglobulin, Thyroid Hormones, Trypsin
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