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Structural/Functional Properties of Human NFU1, an Intermediate [4Fe-4S] Carrier in Human Mitochondrial Iron-Sulfur Cluster Biogenesis.

Abstract
Human mitochondrial NFU1 functions in the maturation of iron-sulfur proteins, and NFU1 deficiency is associated with a fatal mitochondrial disease. We determined three-dimensional structures of the N- and C-terminal domains of human NFU1 by nuclear magnetic resonance spectroscopy and used these structures along with small-angle X-ray scattering (SAXS) data to derive structural models for full-length monomeric apo-NFU1, dimeric apo-NFU1 (an artifact of intermolecular disulfide bond formation), and holo-NFUI (the [4Fe-4S] cluster-containing form of the protein). Apo-NFU1 contains two cysteine residues in its C-terminal domain, and two apo-NFU1 subunits coordinate one [4Fe-4S] cluster to form a cluster-linked dimer. Holo-NFU1 consists of a complex of three of these dimers as shown by molecular weight estimates from SAXS and size-exclusion chromatography. The SAXS-derived structural model indicates that one N-terminal region from each of the three dimers forms a tripartite interface. The activity of the holo-NFU1 preparation was verified by demonstrating its ability to activate apo-aconitase.
AuthorsKai Cai, Gaohua Liu, Ronnie O Frederick, Rong Xiao, Gaetano T Montelione, John L Markley
JournalStructure (London, England : 1993) (Structure) Vol. 24 Issue 12 Pg. 2080-2091 (12 06 2016) ISSN: 1878-4186 [Electronic] United States
PMID27818104 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
CopyrightCopyright © 2016 Elsevier Ltd. All rights reserved.
Chemical References
  • Carrier Proteins
  • Iron-Sulfur Proteins
  • NFU1 protein, human
  • Sulfur
  • Iron
Topics
  • Carrier Proteins (chemistry, metabolism)
  • Humans
  • Iron (metabolism)
  • Iron-Sulfur Proteins (chemistry, metabolism)
  • Mitochondria (chemistry, metabolism)
  • Models, Molecular
  • Nuclear Magnetic Resonance, Biomolecular
  • Protein Structure, Secondary
  • Scattering, Small Angle
  • Sulfur (metabolism)
  • X-Ray Diffraction

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