PXD047733

PXD047733 is an original dataset announced via ProteomeXchange.

Title	FAIMS-enabled N-terminomics analysis reveals novel legumain substrates in murine spleen
Description	Legumain is cysteine protease primarily localised to the endo-lysosomal system. Upregulated legumain activity is associated with inflammation, neurodegeneration, and tumorigenesis. Whilst inhibiting legumain in mouse models has demonstrated therapeutic benefit, the proteolytic mechanisms underpinning its various functions are not well known and thus, further characterisation of its physiological substrates is required. Here, we developed FAIMS-enabled N-terminomics for sensitive and streamlined identification of both protein abundance changes and N-termini in complex samples. Comparison of wildtype and legumain-deficient murine spleens identified 6,366 proteins and 2,528 N-termini, of which 235 were enriched in wildtype spleens. These included 119 with asparaginyl cleavages corresponding to 110 proteins, indicating legumain-specific activity. Surprisingly, many of these localised to the nucleus and cytoplasm, hinting at novel extra-lysosomal roles of legumain. We further confirmed the direct processing of selected substrates by legumain in vitro; together, validating FAIMS-enabled N-terminomics for protease substrate detection in an unbiased and systematic manner.
HostingRepository	PRIDE
AnnounceDate	2024-05-23
AnnouncementXML	Submission_2024-05-22_23:51:27.732.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Alexander Ziegler
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2023-12-11 19:40:40	ID requested
⏵ 1	2024-05-22 23:51:28	announced

10.1016/j.mcpro.2024.100714;

Ziegler AR, Dufour A, Scott NE, Edgington-Mitchell LE, Ion Mobility-Based Enrichment-Free N-Terminomics Analysis Reveals Novel Legumain Substrates in Murine Spleen. Mol Cell Proteomics, 23(2):100714(2024) [pubmed]

submitter keyword: FAIMS,Legumain, protease, N-terminomics

Laura E. Edgington-Mitchell
contact affiliation	Department of Biochemistry and Pharmacology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, Victoria, Australia.
contact email	Laura.EdgingtonMitchell@unimelb.edu.au
lab head
Alexander Ziegler
contact affiliation	University of Melbourne
contact email	azzi@student.unimelb.edu.au
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/2024/05/PXD047733

PRIDE project URI

• PRIDE
  1. PXD047733
     1. Label: PRIDE project
     2. Name: FAIMS-enabled N-terminomics analysis reveals novel legumain substrates in murine spleen