PXD018174-2

PXD018174 is an original dataset announced via ProteomeXchange.

Title	Regulation of titin-based cardiac stiffness by unfolded domain oxidation (UnDOx)
Description	The relationship between oxidative stress and cardiac stiffness is thought to involve modifications to the giant muscle protein titin, which in turn can determine the progression of heart disease. In vitro studies have shown that S-glutathionylation and disulfide bonding of titin fragments could alter the elastic properties of titin; however, whether and where titin becomes oxidized in vivo is less certain. Here we demonstrate, using multiple models of oxidative stress in conjunction with mechanical loading, that immunoglobulin domains preferentially from the distal titin spring region become oxidized in vivo through the mechanism of unfolded domain oxidation (UnDOx). Via oxidation type-specific modification of titin, UnDOx modulates human cardiomyocyte passive force bidirectionally. UnDOx also enhances titin phosphorylation and, importantly, promotes non-constitutive folding and aggregation of unfolded domains. We propose a mechanism whereby UnDOx enables the controlled homotypic interactions within the distal titin spring to stabilize this segment and regulate myocardial passive stiffness.
HostingRepository	PRIDE
AnnounceDate	2020-09-15
AnnouncementXML	Submission_2020-09-20_23:14:45.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Lars Leichert
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	Applied Biosystems cleavable ICAT(TM) heavy; Applied Biosystems cleavable ICAT(TM) light
Instrument	LTQ Orbitrap Elite

Revision	Datetime	Status	ChangeLog Entry
0	2020-03-24 23:17:48	ID requested
1	2020-09-15 05:01:25	announced
⏵ 2	2020-09-20 23:14:46	announced	2020-09-21: Updated publication reference for PubMed record(s): 32929035.
3	2024-10-22 05:12:18	announced	2024-10-22: Updated project metadata.

Loescher CM, Breitkreuz M, Li Y, Nickel A, Unger A, Dietl A, Schmidt A, Mohamed BA, K, ö, tter S, Schmitt JP, Kr, ü, ger M, Kr, ü, ger M, Toischer K, Maack C, Leichert LI, Hamdani N, Linke WA, Regulation of titin-based cardiac stiffness by unfolded domain oxidation (UnDOx). Proc Natl Acad Sci U S A, 117(39):24545-24556(2020) [pubmed]

submitter keyword: Titin, heart muscle, skeletal muscle, redox proteomics, thiol oxidation

Wolfgang A. Linke
contact affiliation	Institute of Physiology II, University of Münster, Münster, Germany
contact email	wlinke@uni-muenster.de
lab head
Lars Leichert
contact affiliation	Ruhr-Universität Bochum
contact email	lars.leichert@ruhr-uni-bochum.de
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/2020/09/PXD018174

PRIDE project URI

• PRIDE
  1. PXD018174
     1. Label: PRIDE project
     2. Name: Regulation of titin-based cardiac stiffness by unfolded domain oxidation (UnDOx)