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| | <SX load='6scj' size='340' side='right' viewer='molstar' caption='[[6scj]], [[Resolution|resolution]] 3.60Å' scene=''> | | <SX load='6scj' size='340' side='right' viewer='molstar' caption='[[6scj]], [[Resolution|resolution]] 3.60Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6scj]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6SCJ OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6SCJ FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6scj]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6SCJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6SCJ FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.6Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TG ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6scj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6scj OCA], [http://pdbe.org/6scj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6scj RCSB], [http://www.ebi.ac.uk/pdbsum/6scj PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6scj ProSAT]</span></td></tr> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6scj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6scj OCA], [https://pdbe.org/6scj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6scj RCSB], [https://www.ebi.ac.uk/pdbsum/6scj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6scj ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/THYG_HUMAN THYG_HUMAN]] Familial thyroid dyshormonogenesis. The disease is caused by mutations affecting the gene represented in this entry. Disease susceptibility is associated with variations affecting the gene represented in this entry. | + | [https://www.uniprot.org/uniprot/THYG_HUMAN THYG_HUMAN] Familial thyroid dyshormonogenesis. The disease is caused by mutations affecting the gene represented in this entry. Disease susceptibility is associated with variations affecting the gene represented in this entry. |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/THYG_HUMAN THYG_HUMAN]] Precursor of the iodinated thyroid hormones thyroxine (T4) and triiodothyronine (T3). | + | [https://www.uniprot.org/uniprot/THYG_HUMAN THYG_HUMAN] Precursor of the iodinated thyroid hormones thyroxine (T4) and triiodothyronine (T3). |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </SX> | | </SX> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Coscia, F]] | + | [[Category: Coscia F]] |
| - | [[Category: Lowe, J]] | + | [[Category: Lowe J]] |
| - | [[Category: Turk, D]] | + | [[Category: Turk D]] |
| - | [[Category: Hormone]]
| + | |
| - | [[Category: Thyroglobulin]]
| + | |
| - | [[Category: Thyroid]]
| + | |
| - | [[Category: Thyroid hormone]]
| + | |
| - | [[Category: Thyroxine]]
| + | |
| - | [[Category: Tri-iodo-thyronine]]
| + | |
| Structural highlights
Disease
THYG_HUMAN Familial thyroid dyshormonogenesis. The disease is caused by mutations affecting the gene represented in this entry. Disease susceptibility is associated with variations affecting the gene represented in this entry.
Function
THYG_HUMAN Precursor of the iodinated thyroid hormones thyroxine (T4) and triiodothyronine (T3).
Publication Abstract from PubMed
Thyroglobulin (TG) is the protein precursor of thyroid hormones, which are essential for growth, development and the control of metabolism in vertebrates(1,2). Hormone synthesis from TG occurs in the thyroid gland via the iodination and coupling of pairs of tyrosines, and is completed by TG proteolysis(3). Tyrosine proximity within TG is thought to enable the coupling reaction but hormonogenic tyrosines have not been clearly identified, and the lack of a three-dimensional structure of TG has prevented mechanistic understanding(4). Here we present the structure of full-length human thyroglobulin at a resolution of approximately 3.5 A, determined by cryo-electron microscopy. We identified all of the hormonogenic tyrosine pairs in the structure, and verified them using site-directed mutagenesis and in vitro hormone-production assays using human TG expressed in HEK293T cells. Our analysis revealed that the proximity, flexibility and solvent exposure of the tyrosines are the key characteristics of hormonogenic sites. We transferred the reaction sites from TG to an engineered tyrosine donor-acceptor pair in the unrelated bacterial maltose-binding protein (MBP), which yielded hormone production with an efficiency comparable to that of TG. Our study provides a framework to further understand the production and regulation of thyroid hormones.
The structure of human thyroglobulin.,Coscia F, Taler-Vercic A, Chang VT, Sinn L, O'Reilly FJ, Izore T, Renko M, Berger I, Rappsilber J, Turk D, Lowe J Nature. 2020 Feb 5. pii: 10.1038/s41586-020-1995-4. doi:, 10.1038/s41586-020-1995-4. PMID:32025030[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Coscia F, Taler-Vercic A, Chang VT, Sinn L, O'Reilly FJ, Izore T, Renko M, Berger I, Rappsilber J, Turk D, Lowe J. The structure of human thyroglobulin. Nature. 2020 Feb 5. pii: 10.1038/s41586-020-1995-4. doi:, 10.1038/s41586-020-1995-4. PMID:32025030 doi:http://dx.doi.org/10.1038/s41586-020-1995-4
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