PXD036463

PXD036463 is an original dataset announced via ProteomeXchange.

Title	A comprehensive set of ER PDI family members supports the biogenesis of pro-inflammatory interleukin 12 family cytokines
Description	Cytokines of the interleukin 12 (IL-12) family are assembled combinatorially from shared alpha and beta subunits. A common theme is that human IL-12 family alpha subunits remain incompletely structured in isolation until they pair with a designate beta subunit. Accordingly, chaperones need to support and control specific assembly processes. Here, we site-specifically introduce photo-crosslinking amino acids into the IL-12 and IL-23 alpha subunits (IL-12alpha and IL-23alpha). This allows to stabilize transient chaperone:client complexes for mass spectrometry and reveals a large set of ER chaperones to interact with IL-12alpha and IL-23alpha. Among those, we focus on protein disulfide isomerase (PDI) family members and reveal IL-12 family subunits to be clients of several ill-characterized PDIs. We find that different PDIs show selectivity for different cysteines in IL-12alpha and IL-23alpha. Despite this, PDI binding generally stabilizes unassembled IL-12alpha and IL-23alpha against degradation. In contrast, alpha:beta assembly appears robust and only multiple simultaneous PDI depletions reduce IL-12 secretion. Our comprehensive analysis of the IL-12/IL-23 chaperone machinery reveals a hitherto uncharacterized role for several PDIs in this process. This extends our understanding of how cells accomplish the task of specific protein assembly reactions for signaling processes. Furthermore, our findings show that cytokine secretion can be modulated by targeting specific ER chaperones.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:32:51.103.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Nina Bach
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	methionine oxidation with neutral loss of 64 Da; mono N-acetylated residue; iodoacetamide derivatized residue
Instrument	timsTOF Pro

Revision	Datetime	Status	ChangeLog Entry
0	2022-09-02 06:25:25	ID requested
1	2022-11-28 01:46:40	announced
⏵ 2	2023-11-14 08:32:54	announced	2023-11-14: Updated project metadata.

Mideksa YG, Aschenbrenner I, Fux A, Kaylani D, Wei, ß CAM, Nguyen TA, Bach NC, Lang K, Sieber SA, Feige MJ, A comprehensive set of ER protein disulfide isomerase family members supports the biogenesis of proinflammatory interleukin 12 family cytokines. J Biol Chem, 298(12):102677(2022) [pubmed]

submitter keyword: interleukin,chaperone, protein disulfide isomerase, protein folding, genetic code expansion

Matthias J. Feige
contact affiliation	Technical University of Munich Department of Chemistry and Institute for Advanced Study Lichtenbergstr. 4 85748 Garching Germany
contact email	matthias.feige@tum.de
lab head
Nina Bach
contact affiliation	TU München
contact email	nina.bach@tum.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD036463
     1. Label: PRIDE project
     2. Name: A comprehensive set of ER PDI family members supports the biogenesis of pro-inflammatory interleukin 12 family cytokines