Two-stage binding of mitochondrial ferredoxin-2 to the core iron-sulfur cluster assembly complex

Ralf Steinhilper, Linda Boß, Sven-A. Freibert, Vinzent Schulz, Nils Krapoth, Susann Kaltwasser, Roland Lill () and Bonnie J. Murphy ()
Additional contact information
Ralf Steinhilper: Max Planck Institute of Biophysics
Linda Boß: Philipps-Universität Marburg
Sven-A. Freibert: Philipps-Universität Marburg
Vinzent Schulz: Philipps-Universität Marburg
Nils Krapoth: Philipps-Universität Marburg
Susann Kaltwasser: Max Planck Institute of Biophysics
Roland Lill: Philipps-Universität Marburg
Bonnie J. Murphy: Max Planck Institute of Biophysics

Nature Communications, 2024, vol. 15, issue 1, 1-14

Abstract: Abstract Iron-sulfur (FeS) protein biogenesis in eukaryotes begins with the de novo assembly of [2Fe-2S] clusters by the mitochondrial core iron-sulfur cluster assembly (ISC) complex. This complex comprises the scaffold protein ISCU2, the cysteine desulfurase subcomplex NFS1-ISD11-ACP1, the allosteric activator frataxin (FXN) and the electron donor ferredoxin-2 (FDX2). The structural interaction of FDX2 with the complex remains unclear. Here, we present cryo-EM structures of the human FDX2-bound core ISC complex showing that FDX2 and FXN compete for overlapping binding sites. FDX2 binds in either a ‘distal’ conformation, where its helix F interacts electrostatically with an arginine patch of NFS1, or a ‘proximal’ conformation, where this interaction tightens and the FDX2-specific C terminus binds to NFS1, facilitating the movement of the [2Fe-2S] cluster of FDX2 closer to the ISCU2 FeS cluster assembly site for rapid electron transfer. Structure-based mutational studies verify the contact areas of FDX2 within the core ISC complex.

Date: 2024
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-024-54585-4 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-54585-4

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-024-54585-4

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().