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.
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Authors | Kai Cai, Gaohua Liu, Ronnie O Frederick, Rong Xiao, Gaetano T Montelione, John L Markley |
Journal | Structure (London, England : 1993)
(Structure)
Vol. 24
Issue 12
Pg. 2080-2091
(12 06 2016)
ISSN: 1878-4186 [Electronic] United States |
PMID | 27818104
(Publication Type: Journal Article, Research Support, N.I.H., Extramural)
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Copyright | Copyright © 2016 Elsevier Ltd. All rights reserved. |
Chemical References |
- Carrier Proteins
- Iron-Sulfur Proteins
- NFU1 protein, human
- Sulfur
- Iron
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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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