FeS-cluster coordination of vertebrate thioredoxins regulates suppression of hypoxia-induced factor 2α through iron regulatory protein 1
Berndt, C.; Hanschmann, E.-M.; Urbainsky, C.; Jordt, L. M.; Mueller, C. S.; Bodnar, Y.; Schippers, S.; Handorf, O.; Nowack, R.; Moulis, J.-M.; Schulzke, C.; Schuenemann, V.; Lillig, C. H.
Show abstract
Iron-regulatory protein 1 (IRP1), a central regulator of iron metabolism in vertebrates, also affects cellular response to hypoxia. IRP1 binds to the iron-responsive element (IRE) in the mRNA encoding hypoxia-inducible factor (HIF) 2, thereby blocking the translation of the HIF2-mRNA, and allowing the transcriptional regulation of, e.g., erythropoiesis. Here, we characterize the oxidoreductase thioredoxin 1 (Trx1) as a new regulator of hypoxia signaling. Human and murine Trx1 complex iron-sulfur clusters using one of the active site cysteinyl residues and a vertebrate-specific additional cysteinyl residue outside the active site. FeS-Trx1 is inactive, activated apo-Trx1 reduces cysteinyl residues in the binding pocket of IRP1/apo-Aconitase 1, which allows IRP1 to bind IREs in regulated mRNAs. Therefore, translation of the HIF2 mRNA requires either sufficient iron supply or the lack of reducing power of the Trx system under iron-limiting conditions. FeS-Trx1 thus links both redox and iron homeostasis to hypoxia responses.
Matching journals
The top 4 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Structural and functional insights into nitrosoglutathione reductase from Chlamydomonas reinhardtii 95%
- The mitochondrial disulphide relay substrate FAM136A safeguards IMS proteostasis and cellular fitness 94%
- An increase in surface hydrophobicity mediates chaperone activity in N-chlorinated proteins 93%
Similar papers in this journal
- X-Ray Structure and enzymatic study of a Bacterial NADPHoxidase highlight the activation mechanism of eukaryoticNOX 95%
- Structure-based electron-confurcation mechanism of the Ldh-EtfAB complex 94%
- A Sec14-like Phosphatidylinositol Transfer Protein Paralog Defines a Novel Class of Heme-binding Proteins With An Unusual Heme Coordination Mechanism 94%
Similar papers in this journal
- Iron-sensing and redox properties of the hemerythrin-like domains of Arabidopsis BRUTUS and BRUTUS-LIKE2 proteins 94%
- The oncogenic CCDC6-RET fusion product is a dual ATP and ADP-dependent kinase that functions via cis-phosphorylation 93%
- Activation mechanism of a small prototypic Rec-GGDEF diguanylate cyclase 92%
Similar papers in this journal
- Free ferrous ions sustain activity of mammalian stearoyl-CoA desaturase-1 95%
- A natural fusion of flavodiiron, rubredoxin, and NADH:rubredoxin oxidoreductase domains is the highly efficient water-forming oxidase of T. vaginalis 94%
- The cation diffusion facilitator protein MamM's cytoplasmic domain exhibits metal-type dependent binding modes and discriminates against Mn2+ 93%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.