PXD025493

PXD025493 is an original dataset announced via ProteomeXchange.

Title	FCGBP, the IgGFc-binding protein, is secreted with all GDPH sequences cleaved, but maintained by inter-fragment disulfide bonds
Description	Mucus has an important protective function and forms a barrier that minimizes the bacterial contact with the colonic epithelium. It is organized as a complex network with several specific proteins of which most are still poorly understood. Abundant proteins in intestinal mucus, in addition to the mucin MUC2, are CLCA1 and FCGBP. FCGBP is expressed in all intestinal goblet cells and secreted into the mucus. It is comprised of repeated von Willebrand Factor D (vWD) domain assemblies, of which most have a GDPH amino acid sequence. This sequence can be autocatalytically cleaved, as previously found in MUC2 and MUC5AC. We show that all vWD with a GDPH sequence are cleaved, and that these cleavages occur early during biosynthesis in the endoplasmic reticulum. All cleaved fragments remained connected by a disulfide bond within each vWD domain. The cleavage can generate a C-terminal reactive Asp-anhydride that could react with other molecules, such as MUC2, but this was not observed. Quantitative analyses by mass spectrometry showed that, in chaotropic solutions, FCGBP was mainly soluble whereas MUC2 was insoluble, and most of the secreted FCGBP was not covalently bound to MUC2. As its name indicates, FCGBP has been suggested to bind IgG, something that was not possible to reproduce in vitro using purified proteins. The function of FCGBP is still unknown, but our results suggest that the Asp-anhydrides do not contribute to covalent crosslinking in the mucin framework nor does FCGBP incorporate IgG in mucus.
HostingRepository	PRIDE
AnnounceDate	2021-06-09
AnnouncementXML	Submission_2021-06-09_09:10:57.423.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Erik Ehrencrona
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2021-04-20 06:33:23	ID requested
⏵ 1	2021-06-09 09:10:57	announced

Dataset with its publication pending

submitter keyword: FCGBP, IgG, GDPH, Mucus

Malin E.V. Johansson
contact affiliation	Department of medical biochemistry and cell biology at Institution of Biomedicine, Gothenburg University
contact email	malin.johansson@medkem.gu.se
lab head
Erik Ehrencrona
contact affiliation	Gothenburg University
contact email	erik.ehrencrona@medkem.gu.se
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/2021/06/PXD025493

PRIDE project URI

• PRIDE
  1. PXD025493
     1. Label: PRIDE project
     2. Name: FCGBP, the IgGFc-binding protein, is secreted with all GDPH sequences cleaved, but maintained by inter-fragment disulfide bonds