Iron–sulfur cluster exchange reactions mediated by the human Nfu protein

By Christine Wachnowsky, Insiya Fidai, J. A. Cowan

July 28, 2017

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Title

Iron–sulfur cluster exchange reactions mediated by the human Nfu protein

Author

Christine Wachnowsky, Insiya Fidai, J. A. Cowan

Year

2016

Journal

Journal of Biological Inorganic Chemistry

Abstract

Human Nfu is an iron–sulfur cluster protein that has recently been implicated in multiple mitochondrial dysfunctional syndrome (MMDS1). The Nfu family of proteins shares a highly homologous domain that contains a conserved active site consisting of a CXXC motif. There is less functional conservation between bacterial and human Nfu proteins, particularly concerning their Iron–sulfur cluster binding and transfer roles. Herein, we characterize the cluster exchange chemistry of human Nfu and its capacity to bind and transfer a [2Fe–2S] cluster. The mechanism of cluster uptake from a physiologically relevant [2Fe–2S](GS)4 cluster complex, and extraction of the Nfu-bound iron–sulfur cluster by glutathione are described. Human holo Nfu shows a dimer-tetramer equilibrium with a protein to cluster ratio of 2:1, reflecting the Nfu-bridging [2Fe–2S] cluster. This cluster can be transferred to apo human ferredoxins at relatively fast rates, demonstrating a direct role for human Nfu in the process of [2Fe–2S] cluster trafficking and delivery.

Full Article

http://link.springer.com/article/10.1007/s00775-016-1381-8

Instrument

J-815

Keywords

Circular dichroism, Kinetics, Ligand binding, Coordination chemistry, Biochemistry