PXD047679 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Higher-order structure and proteoforms of co-occurring C4b-binding protein assemblies in human serum |
Description | The complement is an evolutionarily conserved proteolytic cascade that plays a central role in the innate immune system. To maintain a delicate equilibrium preventing excessive complement activation, complement inhibitors are essential alongside complement activators. One of the major fluid-phase complement inhibitors is C4b-binding protein (C4BP). Human C4BP is a macromolecular glycoprotein composed of three distinct subunits, namely C4BPα, C4BPβ, and vitamin K-dependent protein S (ProS), which form an ensemble of coexisting higher-order structures. Here, we characterize these co-occurring higher-order assemblies of human serum C4BP. We resolve, quantify and characterize isoforms of purified human serum C4BP using distinct single-particle detection techniques: charge detection mass spectrometry, and mass photometry accompanied by high-speed atomic force microscopy. Combining cross-linking mass spectrometry, glycoproteomics, and structural modeling, we report comprehensive glycoproteoform profiles and full-length structural models of the endogenous co-occurring C4BP assemblies, expanding knowledge of this key complement inhibitor’s structure and composition. Finally, we reveal that increased C4BPα to C4BPβ ratio coincides with elevated C-reactive protein levels in patient serum samples. This observation highlights C4BP isoform variation and affirms the distinct role of co-occurring distinct C4BP assemblies upon acute phase inflammation. |
HostingRepository | PRIDE |
AnnounceDate | 2024-05-21 |
AnnouncementXML | Submission_2024-05-21_00:13:51.156.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Tereza Kadavá |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | iodoacetamide derivatized residue |
Instrument | Orbitrap Exploris 480; Orbitrap Fusion |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2023-12-10 14:49:54 | ID requested | |
⏵ 1 | 2024-05-21 00:13:51 | announced | |
Publication List
Keyword List
submitter keyword: C4b-binding protein, mass spectrometry-based techniques, integrative structural modeling,complement |
Contact List
Prof. Albert |
contact affiliation | Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences,University of Utrecht |
contact email | A.J.R.Heck@uu.nl |
lab head | |
Tereza Kadavá |
contact affiliation | Utrecht University, Biomolecular Mass Spectrometry and Proteomics |
contact email | t.kadava@uu.nl |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD047679
- Label: PRIDE project
- Name: Higher-order structure and proteoforms of co-occurring C4b-binding protein assemblies in human serum