PXD047679-1

PXD047679 is an original dataset announced via ProteomeXchange.

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

Revision	Datetime	Status	ChangeLog Entry
0	2023-12-10 14:49:54	ID requested
⏵ 1	2024-05-21 00:13:51	announced

10.1038/S44318-024-00128-Y;

submitter keyword: C4b-binding protein, mass spectrometry-based techniques, integrative structural modeling,complement

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

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PRIDE project URI

• PRIDE
  1. PXD047679
     1. Label: PRIDE project
     2. Name: Higher-order structure and proteoforms of co-occurring C4b-binding protein assemblies in human serum