PXD047461-1

PXD047461 is an original dataset announced via ProteomeXchange.

Title	De novo sequencing of an unknown monoclonal antibody using BU-MS and elucidation of the neutralizing antibody-Streptolysin O complex via cross-linking and hydrogen-deuterium exchange mass spectrometry
Description	The identification of protective epitopes in bacterial pathogens using mass spectrometry proteomics is essential for advancing vaccine design, especially against the backdrop of increasing antibiotic resistance. Our study introduces an innovative strategy, leveraging multi-modal mass spectrometry techniques, to decode the interaction between a neutralizing monoclonal antibody (nAb) and the Streptolysin O (SLO) toxin from Streptococcus pyogenes. By integrating XL-MS, HDX-MS, and computational modeling, we successfully identified and characterized a conserved protective epitope within SLO, providing critical insights for vaccine development. Utilizing a novel nAb sequenced through de novo bottom-up shotgun MS, we explored its binding mechanism and interaction with the SLO antigen with structural proteomics such as XL-MS and HDX-MS. This study not only clarifies the conformational epitope structure but also illuminated the antibody's unique protective mechanism mode. The epitope's high conservation (near 100%) across various S. pyogenes strains underscores its potential as a universal target for vaccine strategies. Additionally, our approach overcomes traditional limitations in epitope mapping, showcasing the power of mass spectrometry in resolving challenging antibody-antigen interfaces. Our findings represent a significant leap in understanding bacterial pathogenesis and immune defense, laying the groundwork for designing next-generation vaccines. The data generated from this study can guide the development of targeted therapies and vaccines, offering new solutions to combat severe streptococcal infections.
HostingRepository	PRIDE
AnnounceDate	2024-05-06
AnnouncementXML	Submission_2024-05-06_09:07:19.755.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Di Tang
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; scientific name: Streptococcus pyogenes MGAS315; NCBI TaxID: 198466;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Eclipse; Q Exactive HF-X; Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2023-12-02 08:43:35	ID requested
⏵ 1	2024-05-06 09:07:20	announced

Tang D, Gueto-Tettay C, Hjortswang E, Str, ö, baek J, Ekstr, ö, m S, Happonen L, Malmstr, ö, m L, Malmstr, ö, m J, Streptolysin O. Anal Chem, 96(22):9060-9068(2024) [pubmed]

10.1021/acs.analchem.4c00596;

submitter keyword: host-pathogen interaction

antibody-antigen binding

mass spectrometry

structural proteomics

Johan Malmström
contact affiliation	Division of Infection Medicine, Department of Clinical Sciences, Faculty of Medicine, Lund University, Klinikgatan 26, 222 42 Lund, Sweden
contact email	johan.malmstrom@med.lu.se
lab head
Di Tang
contact affiliation	Lund University
contact email	di.tang@med.lu.se
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD047461
     1. Label: PRIDE project
     2. Name: De novo sequencing of an unknown monoclonal antibody using BU-MS and elucidation of the neutralizing antibody-Streptolysin O complex via cross-linking and hydrogen-deuterium exchange mass spectrometry