Dityrosine bridge formation and thyroid hormone synthesis are tightly linked and are both dependent on N-glycans

Formation of dityrosine bridges is a ubiquitous process mainly attributed to oxidative stress leading to protein degradation and cellular damages. Here we show that dityrosine formation is involved in a physiological process, thyroid hormone synthesis, and is strictly dependent on structural charact...

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Bibliographic Details
Published in:FEBS letters 1996-11, Vol.396 (2), p.223-226
Main Authors: Baudry, Nathalie, Lejeune, Pierre-Jean, Niccoli, Patricia, Vinet, Liliane, Carayon, Pierre, Mallet, Bernard
Format: Article
Language:English
Subjects:
ConA
concanavalin A
diiodotyrosine
Dimerization
DIT
Dityrosine
Glycosylation
Hormone synthesis
Humans
lactoperoxidase
LPO
Mannose - chemistry
MIT
monoiodotyrosine
Monoiodotyrosine - analysis
Polysaccharides - chemistry
RCA120
Ricinus communis agglutinin
SDS-PAGE
sodium dodecyl sulfate polyacrylamide gel electrophoresis
thyroglobulin
Thyroglobulin - chemistry
Thyroglobulin - metabolism
Thyroid
thyroperoxidase
thyroxine
Thyroxine - biosynthesis
TPO
triiodothyronine
Tyrosine - analogs & derivatives
Tyrosine - chemistry
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Summary:Formation of dityrosine bridges is a ubiquitous process mainly attributed to oxidative stress leading to protein degradation and cellular damages. Here we show that dityrosine formation is involved in a physiological process, thyroid hormone synthesis, and is strictly dependent on structural characteristics, namely N-glycans, presented by the protein acting as the prothyroid hormone. We used two isoforms of the N-terminal thyroid hormone forming domain (NTD) of human thyroglobulin: one without N-glycan (19 kDa isoform) and the other with high mannose type structures (25 kDa isoform). Both isoforms were able to form iodotyrosines after in vitro iodination. However, iodotyrosine coupling to form thyroxine did not occur with the unglycosylated 19 kDa NTD. In contrast, the 25 kDa isoform formed thyroxine. Strikingly, thyroxine synthesis was accompanied by dimerization of the 25 kDa isoform and formation of a dityrosine bridge; none of this was observed with the 19 kDa isoform. Taken as a whole, our results indicate that dimerization through dityrosine bridging accompanies and could have a role in thyroid hormone synthesis.
ISSN:0014-5793
1873-3468
DOI:10.1016/0014-5793(96)01107-6