PXD044285-1

PXD044285 is an original dataset announced via ProteomeXchange.

Title	Investigation of the FcRn:IgG interaction by HDX-MS
Description	Immunoglobulin Gs (IgGs) have become highly successful drug scaffolds by combining very specific target binding with the ability to induce cellular cytotoxicity. Of further advantage, IgGs possess unusually long half-lives in the blood (2-3 week). IgGs achieve such extraordinary half-lives through a pH-dependent interaction with the Neonatal Fc receptor (FcRn) whereby IgGs are recycled. No high-resolution structure of FcRn in complex with a full-length IgG is available, and the interaction was long thought to be mediated solely via the IgG Fc. However, some IgGs with identical Fc parts, but different Fab domains, exhibit different half-lives, suggesting involvement of the Fab domains in FcRn binding. Here, we have employed a combination of HDX-MS and cross-linking MS (XL-MS) to explore the interaction of a full-length IgG with FcRn. HDX-MS and XL-MS analysis confirms an interaction between FcRn and the Fc-domain of IgGs, as a reduction of HDX was observed in both the Fc-domain and FcRn upon complex formation, and three cross-links were identified between FcRn and the Fc-domain. However, FcRn-induced changes in HDX were also observed in the Fab domains, supported by multiple cross-links between the Fab domains and the C-terminal α3 domain of FcRn. Our results thus provide direct evidence for a Fab-FcRn interaction. We envision that these result could advance the engineering of therapeutic IgGs with tailored pharmacokinetics and enhanced efficacy.
HostingRepository	PRIDE
AnnounceDate	2024-12-02
AnnouncementXML	Submission_2024-12-02_14:30:33.503.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Kasper Rand
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Synapt MS

Revision	Datetime	Status	ChangeLog Entry
0	2023-08-02 00:12:06	ID requested
⏵ 1	2024-12-02 14:30:33	announced

Dataset with its publication pending

ProteomeXchange project tag: Hydrogen Deuterium Exchange (HDX-MS)

submitter keyword: MS

Protein-Protein interaction

Mass Spectrometry, HDX-MS

Kasper D. Rand
contact affiliation	Protein Analysis Group, Department of Pharmacy, University of Copenhagen, Copenhagen, Denmark
contact email	kasper.rand@sund.ku.dk
lab head
Kasper Rand
contact affiliation	Department of Pharmacy, University of Copenhagen
contact email	kasper.rand@sund.ku.dk
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/2024/12/PXD044285

PRIDE project URI

• PRIDE
  1. PXD044285
     1. Label: PRIDE project
     2. Name: Investigation of the FcRn:IgG interaction by HDX-MS