PXD026889-1

PXD026889 is an original dataset announced via ProteomeXchange.

Title	The bZIP transcription factor HapX is post-translationally regulated to control iron homeostasis in Aspergillus fumigatus
Description	The 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.
HostingRepository	PRIDE
AnnounceDate	2021-07-20
AnnouncementXML	Submission_2021-07-20_05:47:12.201.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Thomas Krüger
SpeciesList	scientific name: Aspergillus fumigatus; NCBI TaxID: 746128;
ModificationList	ubiquitination signature dipeptidyl lysine; phosphorylated residue; sumoylated lysine; acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive Plus

Revision	Datetime	Status	ChangeLog Entry
0	2021-06-23 09:17:17	ID requested
⏵ 1	2021-07-20 05:47:12	announced

Dataset with its publication pending

submitter keyword: hapX, iron homeostasis, Aspergillus fumigatus, LC-MS/MS, post-translational modifications

Axel A. Brakhage
contact affiliation	Department of Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology - Hans Knöll Institute Jena
contact email	axel.brakhage@leibniz-hki.de
lab head
Thomas Krüger
contact affiliation	Leibniz Institute for Natural Product Research and Infection Biology - Hans Knöll Institute
contact email	thomas.krueger@leibniz-hki.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD026889
     1. Label: PRIDE project
     2. Name: The bZIP transcription factor HapX is post-translationally regulated to control iron homeostasis in Aspergillus fumigatus