The structure of human thyroglobulin

Le résumé fourni par la source

In this extensive work, Coscia et al. determined the molecular architecture of the full-length human thyroglobulin (TG) at high resolution by cryo-electron microscopy and identified the four hormonogenic tyrosine residues which act either as mono- or di-iodotyrosine acceptor and donor sites (A-D) and allow the ultimate step of thyroid hormone synthesis – coupling of two di- or one mono- and one di-iodotyrosine to T4 and T3. The authors validated their structural results by extensive site-directed mutagenesis of human TG, analyzing the hormone synthetic capacity of the mutated TG proteins in vitro. Although distributed in three domains the four donor acceptor sites share structural key features: acceptor donor residues are located in proximity in an antiparallel way and structurally positioned to be solvent-exposed for iodination. Finally, the authors tested the hormone production efficiency of the characterized TG reaction sites outside of the TG structure by transferring them to a bacterial protein by maintaining structural properties of the residues as in the TG monomer. The hormone production of the engineered construct containing the human TG acceptor-donor residues is comparable to that of human TG.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.