PXD058963

PXD058963 is an original dataset announced via ProteomeXchange.

Title	RCL glycosylation of serum corticosteroid-binding globulin: implications in cortisol delivery and septic shock
Description	Corticosteroid-binding globulin (CBG) is a serum glycoprotein that binds and delivers anti-inflammatory cortisol to inflammatory sites through neutrophil elastase (NE)-mediated proteolysis of an exposed reactive centre loop (RCL) on CBG. Timely and tissue-specific delivery of cortisol is critical to alleviate inflammation including in life-threatening septic shock conditions. Important for the cortisol delivery mechanism, which is facilitated by proteolytic cleavage of RCL of CBG and conformational changes to the protein, we recently identified novel O-glycosylation events within the RCL and documented their inhibition of RCL proteolysis (Chernykh et al., 2023). While these observations are of significance as they implicate RCL O-glycosylation as a potential regulator of cortisol delivery, the link to septic shock remains unexplored. To this end, we used mass spectrometry to profile the RCL O-glycosylation of CBG purified from serum of twelve septic shock patients. Serum CBG from all patients exhibited RCL O-glycosylation comprising both sialyl T and/or disialyl T (NeuAc1-2Gal1GalNAc1) O-glycan structures decorating exclusively the Thr342 site. Importantly, relative to less severe cases, individuals presenting with the most severe illness displayed elevated RCL O-glycosylation upon ICU admission, suggesting a previously unknown link to septic shock severity. Overall, we have elucidated RCL O-glycosylation events of serum CBG, which improve our understanding of molecular mechanisms governing the timely and tissue-specific delivery of cortisol to inflammatory sites. The work provides clues to molecular aberrations and disease mechanisms underpinning septic shock.
HostingRepository	PRIDE
AnnounceDate	2025-03-07
AnnouncementXML	Submission_2025-03-07_14:22:17.164.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Anastasia Chernykh
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	complex glycosylation
Instrument	Orbitrap Eclipse; Q Exactive HF-X

Revision	Datetime	Status	ChangeLog Entry
0	2024-12-17 20:50:33	ID requested
⏵ 1	2025-03-07 14:22:17	announced

10.1093/GLYCOB/CWAF013;

submitter keyword: Human serum, septic shock, O-glycosylation, LC-MS/MS

Morten Thaysen-Andersen
contact affiliation	1. School of Natural Sciences, Macquarie University, Sydney, New South Wales, Australia 2. Institute for Glyco-core Research (iGCORE), Nagoya University, Nagoya, Japan
contact email	morten.andersen@mq.edu.au
lab head
Anastasia Chernykh
contact affiliation	Macquarie University
contact email	nayachernykh@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD058963
     1. Label: PRIDE project
     2. Name: RCL glycosylation of serum corticosteroid-binding globulin: implications in cortisol delivery and septic shock