EMD-19359
Structure of the core ISC complex under turnover conditions (frataxin-bound)
EMD-19359
Single-particle2.49 Å
Deposition: 05/01/2024Map released: 18/12/2024
Last modified: 18/12/2024
Sample Organism:
Homo sapiens,
Escherichia coli BL21(DE3)
Sample: Human core ISC complex (NFS1-ISD11-ACP1-ISCU2-FXN/FDX2) under turnover conditions
Fitted models: 8rme (Avg. Q-score: 0.615)
Deposition Authors: Steinhilper R
,
Murphy BJ
Sample: Human core ISC complex (NFS1-ISD11-ACP1-ISCU2-FXN/FDX2) under turnover conditions
Fitted models: 8rme (Avg. Q-score: 0.615)
Deposition Authors: Steinhilper R
,
Murphy BJ
Two-stage binding of mitochondrial ferredoxin-2 to the core iron-sulfur cluster assembly complex.
Steinhilper R ,
Boss L,
Freibert SA,
Schulz V,
Krapoth N,
Kaltwasser S ,
Lill R ,
Murphy BJ
(2024) Nat Commun , 15 , 10559 - 10559
,
Boss L,
Freibert SA,
Schulz V,
Krapoth N,
Kaltwasser S ,
Lill R ,
Murphy BJ
(2024) Nat Commun , 15 , 10559 - 10559
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.
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.