Research interests
Home Research Lab members Teaching
Biogenesis of iron-sulfur proteins
Iron-sulfur
clusters are ubiquitous. They have become integral parts of diverse
physiological processes including energy conversion, nitrogen fixation,
photosynthesis, intracellular iron homeostasis, biosynthesis of heme, biotin
and lipoic acid, RNA modification, amino acid synthesis, protein translation,
DNA replication and repair, and gene expression regulation. Throughout
evolution, organisms have developed a set of highly conserved proteins that are
dedicated for the iron-sulfur cluster assembly in proteins. Deletion of the
iron-sulfur cluster assembly proteins is lethal to organisms, and deficiency of
iron-sulfur cluster assembly has been attributed to a number of human diseases
such as muscle fatigue and Friedreich's ataxia. Using
Escherichia coli as a model system,
we aim to illustrate how iron and sulfide are delivered in concert for the
iron-sulfur cluster assembly in target proteins.
Recent publications:
Yang, J., Tan, G., Zhang, T., White, R. H., Lu, J., & Ding H. (2015) Deletion of the proposed
iron chaperones IscA/SufA results in accumulation of a red intermediate
cysteine desulfurase IscS in Escherichia
coli. J. Biol. Chem. 290, 14226-14234.
Tan, G., Cheng, Z., Peng, Y., Landry, A. P., Lu, J., & Ding,
H. (2014) Copper binding in IscA inhibits iron-sulphur cluster assembly in Escherichia coli. Mol. Microbiol.
93,629-644.
Cheng, Z., Tan, G., Wang, W., Su, X., Landry. A. P., Lu, J., &
Ding, H. (2014) Iron and Zinc Binding Activity of Escherichia coli
Topoisomerase I Homolog YrdD. Biometals, 27, 229-236.
Landry, A. P., Cheng, Z., & Ding, H. (2013) Iron binding is essential for
the function of IscA in iron-sulfur cluster biogenesis. Dalton Trans. 42, 3100-3106.
Wang W, Huang H, Tan G, Si F, Liu M, Landry AP, Lu J, Ding H. (2010) In vivo evidence for the iron binding activity of an iron-sulfur cluster assembly protein IscA in Escherichia coli. Biochem. J. 432, 429-436.
Redox regulation of iron-sulfur proteins
Reduction/oxidation
of iron-sulfur clusters in proteins may lead to subtle conformational change
and subsequently modulate specific activity of the protein. For example, the E. coli DNA-damage-inducible DNA helicase DinG hosts [4Fe-4S]
cluster. We demonstrated that DinG with a reduced [4Fe-4S] cluster is inactive,
and that the DNA helicase activity of DinG is switched on when the reduced
[4Fe-4S] clusters is oxidized by hydrogen peroxide. A recent example is the
human mitochondrial outer membrane protein mitoNEET which contains a [2Fe-2S]
cluster via unusual ligand arrangement of three cysteine and one histidine
residues. Our research has revealed that
the mitoNEET [2Fe-2S] cluster can be reduced by biological thiols and oxidized
by hydrogen peroxide, suggesting that mitoNEET may act as a novel sensor to
oxidative signals to regulate energy metabolism in mitochondria. The goal of
this project is to establish molecular mechanisms for redox regulation of
iron-sulfur proteins in response to oxidative signals.
Recent publications:
Landry, A. P.,
Cheng, Z., & Ding, H. (2015) Reduction of mitochondrial protein mitoNEET
[2Fe-2S] clusters by human glutathione reductase. Free Radic. Biol. Med. 81, 119-127.
Landry, A. P., & Ding, H. (2014) Redox Control of Human
Mitochondrial Outer Membrane Protein MitoNEET [2Fe-2S] Clusters by Biological
Thiols and Hydrogen Peroxide. J. Biol. Chem. 289,
4307-4315.
Tan, G., Landry, A. P., Dai, R., Wang, L., Lu, J., & Ding, H.
(2012) Competition of zinc ion for the [2Fe-2S] cluster binding site in the
diabetes drug target protein mitoNEET. Biometals. 25, 1177-1184.
Cheng, Z., Caillet, A., Ren, B., & Ding, H. (2012) Stimulation
of Escherichia coli DNA damage inducible DNA helicase DinG by the
single-stranded DNA binding protein SSB. FEBS Lett. 586, 3825-3830.
Ren, B. Duan, X. & Ding, H. (2009)
Redox control of the DNA damage-inducible protein DinG helicase activity via
its iron-sulfur cluster. J.
Biol. Chem. 284, 4829-4835.
Nitric
oxide cytotoxicity and iron-sulfur proteins
Nitric
oxide (NO) produced in activated macrophages and neutrophils may act as a
powerful weapon to kill pathogenic bacteria and tumor cells. An excessive production of NO has also been
implicated in causing neurodegenerative disorders, cardiovascular diseases, and
cancers. However, specific targets of NO have not been fully
understood. Recent studies have suggested that iron-sulfur clusters are
the primary target of NO in bacterial cells.
When cells are exposed to NO, a large number of iron-sulfur proteins are
modified forming the protein-bound dinitrosyl iron complexes, resulting in a
prolonged bacteriostasis. Our research
has been focusing on the redox reactions underlying the NO-mediated
modifications of iron-sulfur proteins and the cellular mechanisms for repairing
the NO-modified iron-sulfur proteins.
Recent Publications:
Landry, A. P.
& Ding, H. (2014) The N-terminal domain of human DNA helicase Rtel1
contains a redox active iron-sulfur cluster. Biomed Res Int.
2014:285791.
Landry, A. P., Duan, X., Huang, H., & Ding, H. (2011)
Iron-sulfur Proteins Are the Major Source of Protein-bound Dinitrosyl Iron
Complexes Formed in Escherichia coli Cells under Nitric Oxide Stress. Free
Radic. Biol. Med. 50, 1528-1590.
Yang, J., Duan, X., Landry, A. P. & Ding, H. (2010) Oxygen is required for the L-cysteine-mediated decomposition
of the protein-bound dinitrosyl iron complexes.
Free. Radic. Biol. Med.
49, 268-274.
Duan, X., Yang, J., Ren, B., Tan, G.& Ding, H. (2009)
Reactivity of nitric oxide with the
[4Fe-4S] cluster of dihydroxyacid dehydratase from Escherichia coli. Biochem. J.
417, 783-789.
Ren, B., Zhang, N, Yang, J.& Ding,
H. (2008) Nitric oxide-induced
bacteriostasis and modification of iron-sulphur proteins in Escherichia coli Mol. Microbiol. 70, 953-964.