X-ray snapshots of possible intermediates in the time course of synthesis and degradation of protein-bound Fe₄S₄ clusters

Fe ₄S ₄ clusters are very common versatile prosthetic groups in proteins. Their redox property of being sensitive to O ₂-induced oxidative damage is, for instance, used by the cell to sense oxygen levels and switch between aerobic and anaerobic metabolisms, as exemplified by the fumarate, nitrate re...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2013-04, Vol.110 (18), p.7188-7192
Main Authors: Nicolet, Yvain, Rohac, Roman, Martin, Lydie, Fontecilla-Camps, Juan C.
Format: Article
Language:English
Subjects:
Atoms
Biochemistry, Molecular Biology
Biological Sciences
Crystal structure
Crystallography, X-Ray
Crystals
Ions
Iron-Sulfur Proteins
Iron-Sulfur Proteins - biosynthesis
Iron-Sulfur Proteins - chemistry
Life Sciences
Ligands
Oxidation
Oxygen
Physical Sciences
Protein Binding
Protein Biosynthesis
Proteins
Proteolysis
Structural Biology
Sulfides
Superoxides
Thermotoga maritima
Thermotoga maritima - enzymology
Time Factors
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Summary:Fe ₄S ₄ clusters are very common versatile prosthetic groups in proteins. Their redox property of being sensitive to O ₂-induced oxidative damage is, for instance, used by the cell to sense oxygen levels and switch between aerobic and anaerobic metabolisms, as exemplified by the fumarate, nitrate reduction regulator (FNR). Using the hydrogenase maturase HydE from Thermotoga maritima as a template, we obtained several unusual forms of FeS clusters, some of which are associated with important structural changes. These structures represent intermediate states relevant to both FeS cluster assembly and degradation. We observe one Fe ₂S ₂ cluster bound by two cysteine persulfide residues. This observation lends structural support to a very recent Raman study, which reported that Fe ₄S ₄-to-Fe ₂S ₂ cluster conversion upon oxygen exposure in FNR resulted in concomitant production of cysteine persulfide as cluster ligands. Similar persulfide ligands have been observed in vitro for several other Fe ₄S ₄ cluster-containing proteins. We have also monitored FeS cluster conversion directly in our protein crystals. Our structures indicate that the Fe ₄S ₄-to-Fe ₂S ₂ change requires large structural modifications, which are most likely responsible for the dimer–monomer transition in FNR.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1302388110