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PXD026889

PXD026889 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleThe bZIP transcription factor HapX is post-translationally regulated to control iron homeostasis in Aspergillus fumigatus
DescriptionThe airborne fungus Aspergillus fumigatus causes opportunistic infections in humans with high mortality rates in immunocompromised patients. Previous work established that the bZIP transcription factor HapX is essential for virulence via adaptation to iron limitation by repressing iron-consuming pathways and activating iron acquisition mechanisms, such as the high-affinity siderophore-assisted iron uptake system. Moreover, HapX was shown to be essential for transcriptional activation of vacuolar iron storage and iron-dependent pathways in response to iron availability. Here, we demonstrate that HapX has a very short half-life during iron starvation, which is further decreased in response to iron, while siderophore biosynthetic enzymes are very stable. Immunoprecipitation experiments followed by LC-MS/MS analysis identified Fbx22 and SumO as HapX interactors and, in agreement, HapX post-translational modifications including ubiquitination of lysine161, sumoylation of lysine242 and phosphorylation of threonine319. All three modifications were enriched in the immediate adaptation from iron-limiting to iron-replete conditions. Interfering with these post-translational modifications, either by point mutations or by inactivation, of Fbx22 or SumO, altered HapX degradation, heme biosynthesis and iron resistance to different extents. Consistent with the need to regulate HapX protein levels, overexpression of hapX caused significant growth defects under iron sufficiency. Taken together, our results indicate that post-translational regulation of HapX is important to control iron homeostasis in A. fumigatus.
HostingRepositoryPRIDE
AnnounceDate2021-07-20
AnnouncementXMLSubmission_2021-07-20_05:47:12.201.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterThomas Krüger
SpeciesList scientific name: Aspergillus fumigatus; NCBI TaxID: 746128;
ModificationListubiquitination signature dipeptidyl lysine; phosphorylated residue; sumoylated lysine; acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
InstrumentQ Exactive Plus
Dataset History
RevisionDatetimeStatusChangeLog Entry
02021-06-23 09:17:17ID requested
12021-07-20 05:47:12announced
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: hapX, iron homeostasis, Aspergillus fumigatus, LC-MS/MS, post-translational modifications
Contact List
Axel A. Brakhage
contact affiliationDepartment of Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology - Hans Knöll Institute Jena
contact emailaxel.brakhage@leibniz-hki.de
lab head
Thomas Krüger
contact affiliationLeibniz Institute for Natural Product Research and Infection Biology - Hans Knöll Institute
contact emailthomas.krueger@leibniz-hki.de
dataset submitter
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