PMID: 16679516

 

    Legend: Gene, Sites

Title : A single chondroitin 6-sulfate oligosaccharide unit at Ser-2730 of human thyroglobulin enhances hormone formation and limits proteolytic accessibility at the carboxyl terminus

Abstract :

1. Potential insights into thyroid homeostasis and autoimmunity
2. We localized the site of type D (chondroitin 6-sulfate) oligosaccharide unit addition to human thyroglobulin ( hTg )
3. hTg was chromatographically separated into chondroitin 6-sulfate-containing ( hTg-CS) and chondroitin 6-sulfate-devoid (hTg-CS0) molecules on the basis of their D-glucuronic acid content
4. In an ample number of hTg preparations, the fraction of hTg-CS in total hTg ranged from 32.0 to 71.6%
5. By exploiting the electrophoretic mobility shift and metachromasia conferred by chondroitin 6-sulfate upon the products of limited proteolysis of hTg , chondroitin 6-sulfate was first restricted to a carboxyl-terminal region , starting at residue 2514
6. A single chondroitin 6-sulfate-containing nonapeptide was isolated in pure form from the products of digestion of hTg with endoproteinase Glu-C, and its sequence was determined as LTAGXGLRE ( residues 2726-2734 , X being Ser2730 linked to the oligosaccharide chain)
7. In an in vitro assay of enzymatic iodination, hTg-CS produced higher yields of 3,5,5 '-triiodothyronine (T3) (171%) and 3,5,3',5'-tetraiodothyronine (T4) (134%) than hTg-CS0
8. Unfractionated hTg behaved as hTg-CS
9. Thus, chondroitin 6-sulfate addition to a subset of hTg molecules enhanced the overall level of T4 and, in particular, T3 formation
10. Furthermore, the chondroitin 6-sulfate oligosaccharide unit of hTg-CS protected peptide bond Lys2714-Gly2715 from proteolysis, during the limited digestion of hTg-CS with trypsin
11. These findings provide insights into the molecular mechanism of regulation of the hormonogenic efficiency and of the T4/T3 ratio in hTg
12. The potential implications in the ability of hTg to function as an autoantigen and into the pathogenesis of thyroidal and extra-thyroidal manifestations of autoimmune thyroid disease are discussed

Output (sent_index, trigger, protein, sugar, site):

• 0. Ser-2730, , -, A single chondroitin 6-sulfate oligosaccharide unit, Ser-2730
• 10. hTg-CS, , hTg, the chondroitin 6-sulfate oligosaccharide unit, -

Output(Part-Of) (sent_index, protein, site):

• 0. thyroglobulin, Ser-2730

*Output_Site_Fusion* (sent_index, protein, sugar, site):

• 0. thyroglobulin, A single chondroitin 6-sulfate oligosaccharide unit, Ser-2730

 

Protein	NCBI ID	SENTENCE INDEX