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Reconstitution, characterization, and [2Fe–2S] cluster exchange reactivity of a holo human BOLA3 homodimer

  • Christine Wachnowsky
  • Brian Rao
  • Sambuddha Sen
  • Brian Fries
  • Cecil J. Howard
  • Jennifer J. Ottesen
  • J. A. CowanEmail author
Original Paper
  • 66 Downloads

Abstract

A new class of mitochondrial disease has been identified and characterized as Multiple Mitochondrial Dysfunctions Syndrome (MMDS). Four different forms of the disease have each been attributed to point mutations in proteins involved in iron–sulfur (Fe–S) biosynthesis; in particular, MMDS2 has been associated with the protein BOLA3. To date, this protein has been characterized in vitro concerning its ability to form heterodimeric complexes with two putative Fe–S cluster-binding partners: GLRX5 and NFU. However, BOLA3 has yet to be characterized in its own discrete holo form. Herein we describe procedures to isolate and characterize the human holo BOLA3 protein in terms of Fe–S cluster binding and trafficking and demonstrate that human BOLA3 can form a functional homodimer capable of engaging in Fe–S cluster transfer.

Keywords

BOLA3 Iron–sulfur cluster Cluster transfer Reactivity Homodimer 

Abbreviations

GLRX5

Glutaredoxin 5

CD

Circular dichroism

DTT

Dithiothreitol

FDX

Ferredoxin

GSH

Glutathione

Notes

Acknowledgements

This work was supported by a Grant from the National Institutes of Health [AI072443].

Compliance with ethical standards

Conflict of interest

The authors declare no conflict of interest.

Supplementary material

775_2019_1713_MOESM1_ESM.pdf (574 kb)
Supplementary material 1 (PDF 574 kb)

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Copyright information

© Society for Biological Inorganic Chemistry (SBIC) 2019

Authors and Affiliations

  • Christine Wachnowsky
    • 1
    • 2
  • Brian Rao
    • 1
    • 3
  • Sambuddha Sen
    • 1
  • Brian Fries
    • 1
  • Cecil J. Howard
    • 1
    • 2
  • Jennifer J. Ottesen
    • 1
    • 2
  • J. A. Cowan
    • 1
    • 2
    Email author
  1. 1.Department of Chemistry and BiochemistryThe Ohio State UniversityColumbusUSA
  2. 2.The Ohio State Biochemistry ProgramThe Ohio State UniversityColumbusUSA
  3. 3.Department of Biomedical EngineeringThe Ohio State UniversityColumbusUSA

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