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PXD040428-2

PXD040428 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleUNC-45 assisted myosin folding depends on a conserved FX3HY motif implicated in Freeman Sheldon Syndrome
DescriptionMyosin motors are critical for diverse motility functions ranging from cytokinesis and endocytosis to muscle contraction. The UNC-45 chaperone controls myosin function mediating the folding, assembly, and degradation of the muscle protein. Here, we analyze the molecular mechanism of UNC-45 as a hub in myosin quality control. We show that UNC-45 forms discrete complexes with folded and unfolded myosin, forwarding them to downstream chaperones and E3 ligases. Structural analysis of a minimal chaperone:substrate complex reveals that UNC-45 binds to a conserved FX3HY motif in the myosin motor domain. Disrupting the observed interface by mutagenesis prevents myosin maturation leading to protein aggregation in vivo. We also show that a mutation in the FX3HY motif linked to the Freeman Sheldon Syndrome impairs UNC-45 assisted folding, reducing the level of functional myosin. These findings demonstrate that a faulty myosin quality control is a critical yet unexplored cause of human myopathies.
HostingRepositoryPRIDE
AnnounceDate2024-10-22
AnnouncementXMLSubmission_2024-10-22_06:51:24.191.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterRichard Imre
SpeciesList scientific name: Caenorhabditis elegans; NCBI TaxID: 6239;
ModificationListmonohydroxylated residue; iodoacetamide derivatized residue
InstrumentQ Exactive HF; Orbitrap Fusion Lumos
Dataset History
RevisionDatetimeStatusChangeLog Entry
02023-02-27 05:19:31ID requested
12024-07-25 09:51:58announced
22024-10-22 06:51:24announced2024-10-22: Updated project metadata.
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: UFD-2, myopathy, MHC-B, Myo4,protein quality control, crosslinking mass spectrometry, ubiquitin proteasome system, UNC-45, molecular chaperones, myosin proteostasis
Contact List
Tim Clausen
contact affiliationResearch Institute of Molecular Pathology, Vienna BioCenter, Vienna, Austria
contact emailtim.clausen@imp.ac.at
lab head
Richard Imre
contact affiliationIMBA Vienna
contact emailrichard.imre@imba.oeaw.ac.at
dataset submitter
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Dataset FTP location
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