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PXD053715

PXD053715 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleN-terminomics in NAA10 mutant iPSC-CMs
DescriptionN-terminal-acetyltransferases including NAA10 catalyze N-terminal acetylation (Nt-acetylation), an evolutionarily conserved co- and post-translational modification. However, little is known about the role of Nt-acetylation in cardiac homeostasis. To gain insight into cardiac-dependent NAA10 function, we studied a novel NAA10 variant (p.R4S) segregating with QT-prolongation, cardiomyopathy and developmental delay in a large kindred. Here we show that the NAA10R4S variant reduced enzymatic activity, decreased expression levels of NAA10/NAA15 proteins, and destabilized the enzymatic complex NatA. In NAA10R4S/Y-iPSC-CMs, dysregulation of the late sodium and slow rectifying potassium currents caused severe repolarization abnormalities, consistent with clinical QT prolongation. Engineered heart tissues generated from NAA10R4S/Y-iPSC-CMs had significantly decreased contractile force and sarcomeric disorganization, consistent with the pedigree’s cardiomyopathic phenotype. Proteomic studies revealed dysregulation of metabolic pathways and cardiac structural proteins. We identified small molecule and genetic therapies that normalized the phenotype of NAA10R4S/Y-iPSC-CMs. Our study defines novel roles of Nt-acetylation in cardiac regulation and delineates mechanisms underlying QT prolongation, arrhythmia, and cardiomyopathy caused by NAA10 dysfunction.
HostingRepositoryPRIDE
AnnounceDate2025-02-28
AnnouncementXMLSubmission_2025-02-28_07:54:06.115.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterDaisuke Yoshinaga
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListacetylated residue
InstrumentLTQ Orbitrap Elite
Dataset History
RevisionDatetimeStatusChangeLog Entry
02024-07-06 16:39:54ID requested
12025-02-28 07:54:06announced
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: Human iPSC-CMs
Contact List
Vassilios Bezzerides
contact affiliationDepartment of Cardiology, Boston Children’s Hospital, Harvard Medical School
contact emailVassilios.Bezzerides@cardio.chboston.org
lab head
Daisuke Yoshinaga
contact affiliationBoston Children's Hospital
contact emailDaisuke.Yoshinaga@childrens.harvard.edu
dataset submitter
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Dataset FTP location
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