The pupylation machinery is involved in iron homeostasis by targeting the iron storage protein ferritin

The balance of sufficient iron supply and avoidance of iron toxicity by iron homeostasis is a prerequisite for cellular metabolism and growth. Here we provide evidence that, in Actinobacteria, pupylation plays a crucial role in this process. Pupylation is a posttranslational modification in which th...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2016-04, Vol.113 (17), p.4806-4811
Main Authors: Küberl, Andreas, Polen, Tino, Bott, Michael
Format: Article
Language:English
Subjects:
Adenosine Triphosphatases - metabolism
Bacteria
Bacterial Proteins - metabolism
Biological Sciences
Corynebacterium - metabolism
Eukaryotes
Ferritins - metabolism
Homeostasis
Homeostasis - physiology
Iron
Iron - metabolism
Models, Biological
Proteasome Endopeptidase Complex - metabolism
Protein Binding
Protein Processing, Post-Translational - physiology
Proteins
Toxicity
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Summary:The balance of sufficient iron supply and avoidance of iron toxicity by iron homeostasis is a prerequisite for cellular metabolism and growth. Here we provide evidence that, in Actinobacteria, pupylation plays a crucial role in this process. Pupylation is a posttranslational modification in which the prokaryotic ubiquitin-like protein Pup is covalently attached to a lysine residue in target proteins, thus resembling ubiquitination in eukaryotes. Pupylated proteins are recognized and unfolded by a dedicated AAA+ ATPase (Mycobacterium proteasomal AAA+ ATPase; ATPase forming ring-shaped complexes). In Mycobacteria, degradation of pupylated proteins by the proteasome serves as a protection mechanism against several stress conditions. Other bacterial genera capable of pupylation such as Corynebacterium lack a proteasome, and the fate of pupylated proteins is unknown. We discovered that Corynebacterium glutamicum mutants lacking components of the pupylation machinery show a strong growth defect under iron limitation, which was caused by the absence of pupylation and unfolding of the iron storage protein ferritin. Genetic and biochemical data support a model in which the pupylation machinery is responsible for iron release from ferritin independent of degradation.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1514529113