PXD062462

PXD062462 is an original dataset announced via ProteomeXchange.

Title	Molecular recognition of thyroglobulin by sortilin
Description	Sortilin is a ubiquitous membrane receptor mediating protein trafficking along different cellular routes. In the thyroid gland, sortilin was proposed as a post-endocytic receptor of the thyroid hormone precursor, thyroglobulin (TG). It was reported that sortilin preferably shuttles iodinated TG to the lysosome, thereby facilitating the proteolytic release of thyroid hormones. However, the molecular details of this interaction are unknown. In this work, using an integrative approach, we reveal the structural basis of human TG recognition by sortilin. We found that sortilin interacts with a TG C-terminal peptide, which is more exposed in the monomeric TG than in its commonly found dimeric form. Unlike previously hypothesised, we suggest that the TG iodination state does not affect interaction with sortilin, which could act as a scavenger for degraded TG, as proposed for other cargoes. By comparing the mode of binding of TG and other known sortilin partners, we then derived a consensus ligand recognition motif. Overall, this study broadens understanding on the role of sortilin in TG trafficking and provides insight into general signatures for sortilin cargoes in other tissues.
HostingRepository	PRIDE
AnnounceDate	2026-01-27
AnnouncementXML	Submission_2026-01-27_05:01:34.978.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD062462
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Alessio Di Ianni
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2025-04-01 06:48:25	ID requested
⏵ 1	2026-01-27 05:01:35	announced

10.6019/PXD062462;

10.1038/S41467-026-68658-Z;

submitter keyword: thyroid, sortilin, cryo-EM,thyroglobulin, cross-linking mass spectrometry, crosslinking mass spectrometry, crosslinking MS, trafficking, XL-MS, iodination, endocytosis

Andrea Graziadei
contact affiliation	Fondazione Human Technopole
contact email	andrea.graziadei@fht.org
lab head
Alessio Di Ianni
contact affiliation	Human Technopole
contact email	alessio.diianni@fht.org
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD062462
     1. Label: PRIDE project
     2. Name: Molecular recognition of thyroglobulin by sortilin