Abstract:
:Hundreds of cellular proteins require iron cofactors for activity, and cells express systems for their assembly and distribution. Molecular details of the cytosolic iron pool used for iron cofactors are lacking, but iron chaperones of the poly(rC)-binding protein (PCBP) family play a key role in ferrous ion distribution. Here we show that, in cells and in vitro, PCBP1 coordinates iron via conserved cysteine and glutamate residues and a molecule of noncovalently bound glutathione (GSH). Proteomics analysis of PCBP1-interacting proteins identified BolA2, which functions, in complex with Glrx3, as a cytosolic [2Fe-2S] cluster chaperone. The Fe-GSH-bound form of PCBP1 complexes with cytosolic BolA2 via a bridging Fe ligand. Biochemical analysis of PCBP1 and BolA2, in cells and in vitro, indicates that PCBP1-Fe-GSH-BolA2 serves as an intermediate complex required for the assembly of [2Fe-2S] clusters on BolA2-Glrx3, thereby linking the ferrous iron and Fe-S distribution systems in cells.
journal_name
Nat Chem Bioljournal_title
Nature chemical biologyauthors
Patel SJ,Frey AG,Palenchar DJ,Achar S,Bullough KZ,Vashisht A,Wohlschlegel JA,Philpott CCdoi
10.1038/s41589-019-0330-6subject
Has Abstractpub_date
2019-09-01 00:00:00pages
872-881issue
9eissn
1552-4450issn
1552-4469pii
10.1038/s41589-019-0330-6journal_volume
15pub_type
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