A conserved acidic residue drives thyroxine synthesis within thyroglobulin and other protein precursors.

ABSTRACT: Thyroxine, the main hormone product of the thyroid, is produced at multiple sites within its protein precursor thyroglobulin. Each site consists of two tyrosine residues which undergo iodination and coupling, resulting in the synthesis of thyroxine at the acceptor tyrosine, where the hormone synthesis is later completed by proteolysis. Within the structurally resolved sites, the role of an essential conserved acidic residue preceding the acceptor remains elusive. To elucidate the mechanism of thyroxine synthesis we engineered a single-site minimal protein precursor. First, by its in vitro iodination and site-directed mutagenesis we show that the presence of the acidic residue, preferably glutamate, favors thyroxine synthesis. Secondly, within the designed precursor, we computationally mode

SUBMITTER: Stejskalova C 

PROVIDER: S-EPMC11730217 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature