Molecular recognition of thyroglobulin by sortilin.

ABSTRACT: Sortilin is a ubiquitous membrane receptor mediating trafficking of protein cargoes. In the thyroid, sortilin binds thyroglobulin (TG) during its endocytosis, a key process in thyroid homeostasis. Although sortilin has been proposed to recognise highly iodinated TG, the molecular details of this interaction remain unknown. In this work, using an integrative structural biology approach, we reveal that sortilin binds an unstructured TG C-terminal peptide and exhibits a strong preference for the monomeric TG over the commonly known dimeric form. We find that sortilin-TG interaction is independent of the iodination state of TG and instead relies on the conversion to its monomeric state, presumably promoted by extracellular degradation. Furthermore, using AlphaPulldown and sequence analysis, we

SUBMITTER: Boniardi I 

PROVIDER: S-EPMC12936070 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature