PXD065112

PXD065112 is an original dataset announced via ProteomeXchange.

Title	Molecular basis of Fab-dependent IgA antibody recognition by gut-associated metallopeptidases
Description	Immunoglobulin A (IgA) is essential for mucosal immunity and is implicated in autoimmune diseases like IgA nephropathy (IgAN). Certain pathogenic and commensal bacteria produce IgA proteases (IgAPs) that selectively cleave IgA, potentially aiding bacterial colonization and offering therapeutic avenues for IgAN. Here, we investigate the substrate specificity of M64 family peptidases, focusing on the IgAP ThomasA from Thomasclavelia ramosa and BF3526 from Bacteroides fragilis. Structural, biochemical, and mutagenesis data demonstrate that ThomasA cleaves IgA through exclusive recognition of the Fab region—a mechanism distinct from other antibody-specific peptidases, which typically require engagement of the Fc region. In contrast, X-ray crystal structures of BF3526 in complex with substrate and product peptides, together with enzymology assays, show that this enzyme targets the N-terminus of predigested proteins. These findings reveal divergent substrate recognition strategies within the M64 family and provide structural insight into their conserved catalytic mechanism. Together, they enhance our understanding of bacterial adaptation and support the rational design of enzymes for IgA-mediated autoimmune diseases. The LC-MS data associated with the project is included in the current dataset.
HostingRepository	PRIDE
AnnounceDate	2025-08-08
AnnouncementXML	Submission_2025-08-08_04:59:16.313.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Andrea Persson
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	impact II

Revision	Datetime	Status	ChangeLog Entry
0	2025-06-17 06:02:56	ID requested
⏵ 1	2025-08-08 04:59:17	announced

10.1038/s44318-025-00518-w;

M, á, rquez-Mo, ñ, ino M Á, Mart, í, nez Gascue, ñ, a A, Azzam T, Persson A, Manzanares-Gomez A, Aguillo-Urarte M, Brown TT, Montero-Sagarminaga A, Lood R, Naegeli A, Connell SR, Sastre DE, Sundberg EJ, Trastoy B, Molecular basis of Fab-dependent IgA antibody recognition by gut-bacterial metallopeptidases. EMBO J, ():(2025) [pubmed]

submitter keyword: IgA, IgA protease, metallopeptidase

Beatrice Trastoy
contact affiliation	Structural Glycoimmunology Laboratory, BiobizkaiaHealth Research Institute, Barakaldo, Spain
contact email	beatriz.trastoy@gmail.com
lab head
Andrea Persson
contact affiliation	Genovis AB
contact email	andrea.persson@genovis.com
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/2025/08/PXD065112

PRIDE project URI

• PRIDE
  1. PXD065112
     1. Label: PRIDE project
     2. Name: Molecular basis of Fab-dependent IgA antibody recognition by gut-associated metallopeptidases