A PCBP1-BolA2 chaperone complex delivers iron for cytosolic [2Fe-2S] cluster assembly.

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 Biol

journal_title

Nature chemical biology

authors

Patel SJ,Frey AG,Palenchar DJ,Achar S,Bullough KZ,Vashisht A,Wohlschlegel JA,Philpott CC

doi

10.1038/s41589-019-0330-6

subject

Has Abstract

pub_date

2019-09-01 00:00:00

pages

872-881

issue

9

eissn

1552-4450

issn

1552-4469

pii

10.1038/s41589-019-0330-6

journal_volume

15

pub_type

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