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PXD029770

PXD029770 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleDynamic Assembly of the Cytosolic Iron-Sulfur Cluster Biogenesis Machinery Requires Iron-Sulfur Cluster Incorporation of CIAO3
DescriptionCytosolic iron-sulfur (Fe-S) cluster assembly (CIA) pathway delivers Fe-S clusters to nuclear and cytosolic Fe-S proteins involved in essential cellular functions. This delivery process is regulated by availability of iron and oxygen, but it remains unclear how CIA components orchestrate the cluster transfer under varying cellular environments. Here, we investigated the organization of CIA machinery under various conditions. We developed a targeted proteomics assay monitoring known CIA factors. Using this assay, we were able to detect NUBP1, CIAO3 and CIA substrates in immunoprecipitates of NUBP2, a component of the CIA scaffold complex. We also revealed that NUBP2 transiently associates with the CIA targeting complex (MMS19, CIAO1, CIAO2B), indicating the possible existence of CIA metabolons. We observed stronger interactions between CIAO3 and the CIA scaffold complex upon iron supplementation or low oxygen tension, while iron chelation and reactive oxygen species weaken CIAO3 interactions with CIA components. We further demonstrated that CIAO3 mutant with defective Fe-S cluster binding failed to integrate into the metabolons. However, these mutants unexpectedly exhibit stronger association with CIA substrates regardless of their reduced association with the CIA targeting complex, implicating that CIAO3 and CIA substrates may present in complexes independent of the CIA targeting complex. Together, our data suggested that CIA components potentially form metabolons whose assembly are regulated by environmental cues and require Fe-S cluster incorporation in CIAO3. These findings provided additional evidence that the CIA pathway adapts to changes in cellular environment through complex reorganization.
HostingRepositoryMassIVE
AnnounceDate2022-05-29
AnnouncementXMLSubmission_2022-05-29_10:36:10.130.xml
DigitalObjectIdentifier
ReviewLevelNon peer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportSupported dataset by repository
PrimarySubmitterXiaorui Fan
SpeciesList scientific name: Homo sapiens; common name: human; NCBI TaxID: 9606;
ModificationListCarbamidomethyl
InstrumentOrbitrap Fusion Lumos
Dataset History
RevisionDatetimeStatusChangeLog Entry
02021-11-16 10:50:54ID requested
12022-05-29 10:36:10announced
Publication List
no publication
Keyword List
submitter keyword: iron-sulfur cluster biogenesis, targeted proteomics assay, protein-protein interaction
Contact List
James A Wohlschlegel
contact affiliationUCLA Biological Chemistry
contact emailjwohl@ucla.edu
lab head
Xiaorui Fan
contact affiliationUCLA
contact emailxfbubu@gmail.com
dataset submitter
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MassIVE dataset URI
Dataset FTP location
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