PXD043347

PXD043347 is an original dataset announced via ProteomeXchange.

Title	Epitope and Paratope Mapping of TNFα/Infliximab complex by cross-linking mass spectrometry and integrative modeling reveals high level of interaction specificity
Description	Mass spectrometry (MS) has become one of the core technologies to study protein structures, protein-ligand and protein-protein interactions. Chemical cross-linking combined with mass spectrometry (XL-MS) is quickly spreading over different biochemistry laboratories for the continuous increase of its biological applications and standardized protocols that make it attractive for academia and industry research scientists. In recent years, XL-MS has developed as a powerful technique in structural biology, from studying structures of purified proteins in vitro to deciphering intricate protein-protein interaction (PPI) networks in cells, organelles and tissues on a system-wide scale. However, the number of XL-MS studies for the inves-tigation of epitope/paratope mapping of antigen-antibody complexes is still limited up to now. In this manuscript, we devel-oped a simple, fast and automated workflow to define the interaction interface between the chimeric antibody Infliximab (IFX) and its own target, the Tumor Necrosis Factor alpha (TNFα). This workflow integrates XL-MS data to identify areas in proximity to the binding regions and epitope/paratope probability calculation to pinpoint the antigen-antibody binding sites. The data are combined to generate refined 3D models of the antigen-antibody complex which closely resemble the X-ray IFX/TNFα structure and capture their correct interaction surface. The present workflow can be applied to investigate any antigen-antibody complex, even when no previous structural knowledge is available. This strategy is a fascinating oppor-tunity to thoroughly characterize antigen-antibody interactions and to allow the understanding of their binding mechanisms in order to properly design better antibody therapeutics in the future
HostingRepository	PRIDE
AnnounceDate	2024-02-27
AnnouncementXML	Submission_2024-02-27_07:34:05.767.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Andrea Di Ianni
SpeciesList	scientific name: Escherichia coli; NCBI TaxID: 562;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2023-06-27 10:28:17	ID requested
⏵ 1	2024-02-27 07:34:06	announced

10.1021/acs.jproteome.3c00816;

Di Ianni A, Di Ianni A, Cowan K, Barbero LM, Sirtori FR, Leveraging Cross-Linking Mass Spectrometry for Modeling Antibody-Antigen Complexes. J Proteome Res, 23(3):1049-1061(2024) [pubmed]

submitter keyword: Cross-linking mass spectrometry

Monoclonal antibodies

Integrative modeling

Epitope/Paratope mapping

Luca Barbero
contact affiliation	NBE-DMPK Innovative BioAnalytics, Merck Serono RBM S.p.A., an affiliate of Merck KGaA, Darmstadt, Germany, Via Ribes 1, 10010 Colleretto Giacosa (TO)
contact email	luca.barbero@merckgroup.com
lab head
Andrea Di Ianni
contact affiliation	Merck KGaA
contact email	andrea.di-ianni@external.merckgroup.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/2024/02/PXD043347

PRIDE project URI

• PRIDE
  1. PXD043347
     1. Label: PRIDE project
     2. Name: Epitope and Paratope Mapping of TNFα/Infliximab complex by cross-linking mass spectrometry and integrative modeling reveals high level of interaction specificity