5WKP

Crystal Structure of the Human mitochondrial Cysteine Desulfurase in complex with ISD11 and Iron-Sulfur Cluster Scaffold Protein ISCU1, and E. coli ACP1 protein at 3.15A


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.15 Å
  • R-Value Free: 0.242 
  • R-Value Work: 0.186 
  • R-Value Observed: 0.190 

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Literature

Structure and functional dynamics of the mitochondrial Fe/S cluster synthesis complex.

Boniecki, M.T.Freibert, S.A.Muhlenhoff, U.Lill, R.Cygler, M.

(2017) Nat Commun 8: 1287-1287

  • DOI: https://doi.org/10.1038/s41467-017-01497-1
  • Primary Citation of Related Structures:  
    5WGB, 5WKP, 5WLW

  • PubMed Abstract: 

    Iron-sulfur (Fe/S) clusters are essential protein cofactors crucial for many cellular functions including DNA maintenance, protein translation, and energy conversion. De novo Fe/S cluster synthesis occurs on the mitochondrial scaffold protein ISCU and requires cysteine desulfurase NFS1, ferredoxin, frataxin, and the small factors ISD11 and ACP (acyl carrier protein). Both the mechanism of Fe/S cluster synthesis and function of ISD11-ACP are poorly understood. Here, we present crystal structures of three different NFS1-ISD11-ACP complexes with and without ISCU, and we use SAXS analyses to define the 3D architecture of the complete mitochondrial Fe/S cluster biosynthetic complex. Our structural and biochemical studies provide mechanistic insights into Fe/S cluster synthesis at the catalytic center defined by the active-site Cys of NFS1 and conserved Cys, Asp, and His residues of ISCU. We assign specific regulatory rather than catalytic roles to ISD11-ACP that link Fe/S cluster synthesis with mitochondrial lipid synthesis and cellular energy status.


  • Organizational Affiliation

    Department of Biochemistry, University of Saskatchewan, 107 Wiggins Road, Saskatoon, SK, Canada, S7N 5E5.


Macromolecules
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Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Cysteine desulfurase, mitochondrial
A, E
406Homo sapiensMutation(s): 0 
Gene Names: NFS1NIFSHUSSY-08
EC: 2.8.1.7
UniProt & NIH Common Fund Data Resources
Find proteins for Q9Y697 (Homo sapiens)
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Go to UniProtKB:  Q9Y697
PHAROS:  Q9Y697
GTEx:  ENSG00000244005 
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UniProt GroupQ9Y697
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  • Reference Sequence
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Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
LYR motif-containing protein 4
B, F
91Homo sapiensMutation(s): 1 
Gene Names: LYRM4C6orf149ISD11CGI-203
UniProt & NIH Common Fund Data Resources
Find proteins for Q9HD34 (Homo sapiens)
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PHAROS:  Q9HD34
GTEx:  ENSG00000214113 
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UniProt GroupQ9HD34
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Entity ID: 3
MoleculeChains Sequence LengthOrganismDetailsImage
Acyl carrier protein
C, G
77Escherichia coliMutation(s): 0 
Gene Names: acpPECS88_1108
UniProt
Find proteins for P0A6A8 (Escherichia coli (strain K12))
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UniProt GroupP0A6A8
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  • Reference Sequence
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Entity ID: 4
MoleculeChains Sequence LengthOrganismDetailsImage
Iron-sulfur cluster assembly enzyme ISCU, mitochondrial
D, H
150Homo sapiensMutation(s): 1 
Gene Names: ISCUNIFUN
UniProt & NIH Common Fund Data Resources
Find proteins for Q9H1K1 (Homo sapiens)
Explore Q9H1K1 
Go to UniProtKB:  Q9H1K1
PHAROS:  Q9H1K1
GTEx:  ENSG00000136003 
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UniProt GroupQ9H1K1
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  • Reference Sequence
Small Molecules
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.15 Å
  • R-Value Free: 0.242 
  • R-Value Work: 0.186 
  • R-Value Observed: 0.190 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 98.36α = 90
b = 123.29β = 90
c = 151.724γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
XDSdata reduction
XDSdata scaling
PHASERphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2017-11-15
    Type: Initial release
  • Version 1.1: 2023-10-04
    Changes: Data collection, Database references, Refinement description