Proteomics

Dataset Information

0

Investigation of the FcRn:IgG interaction by HDX-MS


ABSTRACT: 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.

INSTRUMENT(S): Synapt MS

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Kasper Rand  

LAB HEAD: Kasper D. Rand

PROVIDER: PXD044285 | Pride | 2024-12-02

REPOSITORIES: Pride

Dataset's files

Source:
Action DRS
DS1_FcRn_long.zip Other
DS2_FcRn_short.zip Other
DS3_Cmab.zip Other
DS4_HmAb.zip Other
DynamX_files.zip Other
Items per page:
1 - 5 of 10

Similar Datasets

2020-10-26 | PXD014710 | Pride
2021-11-29 | PXD029321 | Pride
2023-10-24 | PXD039049 | Pride
2024-05-22 | PXD047910 | Pride
2019-09-11 | GSE129272 | GEO
2023-03-11 | PXD033645 | Pride
2024-08-28 | GSE255950 | GEO
2024-03-20 | GSE254483 | GEO
2023-12-18 | GSE246602 | GEO
2024-01-16 | PXD039462 | JPOST Repository