PXD047044

PXD047044 is an original dataset announced via ProteomeXchange.

Title	Peptidylarginine deiminase 2 citrullinates MZB1 and promotes the secretion of IgM and IgA
Description	MZB1 is an endoplasmic reticulum residential protein preferentially expressed in plasma cells, marginal zone and B1 B cells. Recent studies on murine B cells shows that it interacts with the tail piece of IgM and IgA heavy chain and promotes the secretion of these two classes of immunoglobulin. However, its role in primary human B cells has yet to be determined and how its function is regulated is still unknown. The conversion of peptidylarginine to peptidycitrulline, also known as citrullination, by peptidylarginine deiminases (PADs) can critically influence the function of proteins in immune cells, such as neutrophils and T cells; however, the role of PADs in B cells remains to be elucidated. In an unbiased analysis of the human citrullinomeic analysis, we found that MZB1 was preferentially enriched in the pool of citrullinated lung proteins obtained from patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD) compared to those from idiopathic pulmonary fibrosis or chronic obstructive pulmonary diseases. The citrullination of MZB1 was confirmed with mass spectrometry, in vitro citrullination, and binding by phenylglyoxal in the absence or presence of a PAD2-specific inhibitor AFM-30a. Ablation or pharmacological inhibition of PAD2 in primary human B cells attenuated the secretion of IgM and IgA but not IgG or the differentiation of IgM or IgA-expressing plasmablasts, recapitulating the effect of ablating MZB1. In addition, the physical interaction between endogenous MZB1 and IgM/IgA was attenuated by AFM-30a. Taken together, our data confirm the function of MZB1 in primary human plasmablasts and suggest that PAD2 promotes IgM/IgA secretion by citrullinating MZB1, thereby contributing to the pathogenesis of rheumatoid arthritis and RA-ILD.
HostingRepository	PRIDE
AnnounceDate	2023-11-23
AnnouncementXML	Submission_2023-11-23_08:13:05.038.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Paul Thompson
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	LTQ Orbitrap

Revision	Datetime	Status	ChangeLog Entry
0	2023-11-17 14:10:07	ID requested
⏵ 1	2023-11-23 08:13:05	announced

10.3389/FIMMU.2023.1290585;

submitter keyword: post-translational modification,citrullination, MZB1, rheumatoid arthritis

Paul R Thompson
contact affiliation	UMass Chan Medical School
contact email	paul.thompson@umassmed.edu
lab head
Paul Thompson
contact affiliation	Univeristy of Massachusetts Medical School
contact email	paul.thompson@umassmed.edu
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2023/11/PXD047044

PRIDE project URI

• PRIDE
  1. PXD047044
     1. Label: PRIDE project
     2. Name: Peptidylarginine deiminase 2 citrullinates MZB1 and promotes the secretion of IgM and IgA