PXD029013

PXD029013 is an original dataset announced via ProteomeXchange.

Title	Cryo-EM structure of native human thyroglobulin
Description	The Tthyroglobulin (Tg) protein is the essential fundament toto thyroid hormone synthesis, a key player playing a vital role in the regulation of metabolism, development and growth and serving as intraglandular iodine storage. Its structure is conserved among vertebrates. Tg is delivered through the secretory pathway of the thyroid follicular unit to the central colloid depository, where it is iodinated at specific tyrosine sites to form mono- or diiodotyrosine, which combine to produce triiodothyronine (T3) and thyroxine (T4), respectively. Synthesis of these hormones depends on the precise 3D structure, iodination capacity and post-translational modification of Tg. The Tg structure is overall conserved among vertebrates and , which and structural information has long been remained unknown missing despite decades of research until recently structural information has been made available on human thyroglobulin (hTg) originating from recombinant hTg and endogenous hTg from patients with goitres. Here, we present the cryo-electron microscopy structure of native and fully functional human thyroglobulin (hTg) originating from healthy human thyroid glands, to a global resolution of 3.2 Å. We used LC-MS experiments to The structure provides detailed information on the location of the hTg hormonogenic sites by revealing native iodination, and reveals the position as well as the role of many of its glycosylation sites and other post-translational modifications. Our results offer structural insights into thyroid hormonogenesis of natively functional hTg and provide a fundamental understanding of clinically relevant hTg mutations, which can improve treatment of thyroid diseases.
HostingRepository	PRIDE
AnnounceDate	2022-02-17
AnnouncementXML	Submission_2022-02-17_00:28:26.337.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD029013
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Alexander Schmidt
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2021-10-08 06:49:12	ID requested
⏵ 1	2022-02-17 00:28:27	announced

Adaixo R, Steiner EM, Righetto RD, Schmidt A, Stahlberg H, Taylor NMI, Cryo-EM structure of native human thyroglobulin. Nat Commun, 13(1):61(2022) [pubmed]

submitter keyword: thyroglobulin, human, LC-MS

Alexander Scxhmidt
contact affiliation	Proteopmics Core Facility, Biozentrum,Univeristy of Basel, Switzerland
contact email	alex.schmidt@unibas.ch
lab head
Alexander Schmidt
contact affiliation	Proteomics Core Facility
contact email	alex.schmidt@unibas.ch
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD029013
     1. Label: PRIDE project
     2. Name: Cryo-EM structure of native human thyroglobulin