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Molecular architecture of thyroglobulin revealed 期刊论文
NATURE, 2020, 578 (7796) : 520-521
作者:  Botvinik-Nezer, Rotem;  Holzmeister, Felix;  Camerer, Colin F.;  Dreber, Anna;  Huber, Juergen;  Johannesson, Magnus;  Kirchler, Michael;  Iwanir, Roni;  Mumford, Jeanette A.;  Adcock, R. Alison;  Avesani, Paolo;  Baczkowski, Blazej M.;  Bajracharya, Aahana
收藏  |  浏览/下载:11/0  |  提交时间:2020/07/03

The structure of thyroglobulin, the enormous protein that acts as a precursor for thyroid hormones, has been determined, and its hormone-forming tyrosine amino-acid residues have been identified.


Fresh insight into the biosynthesis of thyroid hormones.


  
The structure of human thyroglobulin 期刊论文
NATURE, 2020, 578 (7796) : 627-+
作者:  Golub, Eyal;  Subramanian, Rohit H.;  Esselborn, Julian;  Alberstein, Robert G.;  Bailey, Jake B.;  Chiong, Jerika A.;  Yan, Xiaodong;  Booth, Timothy;  Baker, Timothy S.;  Tezcan, F. Akif
收藏  |  浏览/下载:13/0  |  提交时间:2020/07/03

The cryo-electron microscopy structure of human thyroglobulin reveals that proximity, flexibility and solvent exposure are key characteristics of its hormonogenic tyrosine pairs, and provides a framework for understanding the formation of thyroid hormones.


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 angstrom, 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.


  
Ocean acidification increases iodine accumulation in kelp-based coastal food webs 期刊论文
GLOBAL CHANGE BIOLOGY, 2019, 25 (2) : 629-639
作者:  Xu, Dong;  Brennan, Georgina;  Xu, Le;  Zhang, Xiao W.;  Fan, Xiao;  Han, Wen T.;  Mock, Thomas;  McMinn, Andrew;  Hutchins, David A.;  Ye, Naihao
收藏  |  浏览/下载:8/0  |  提交时间:2019/04/09
iodine metabolism  kelp  ocean acidification  Saccharina japonica  thyroid hormone  vanadium-dependent haloperoxidase