Abstract
Iron–sulfur clusters are ubiquitous in biology and function in electron transfer and catalysis. They are assembled from iron and cysteine sulfur on protein scaffolds. Iron is typically stored as iron oxyhydroxide, ferrihydrite, encapsulated in 12 nm shells of ferritin, which buffers cellular iron availability. Here we have characterized IssA, a protein that stores iron and sulfur as thioferrate, an inorganic anionic polymer previously unknown in biology. IssA forms nanoparticles reaching 300 nm in diameter and is the largest natural metalloprotein complex known. It is a member of a widely distributed protein family that includes nitrogenase maturation factors, NifB and NifX. IssA nanoparticles are visible by electron microscopy as electron-dense bodies in the cytoplasm. Purified nanoparticles appear to be generated from 20 nm units containing ∼6,400 Fe atoms and ∼170 IssA monomers. In support of roles in both iron–sulfur storage and cluster biosynthesis, IssA reconstitutes the [4Fe-4S] cluster in ferredoxin in vitro.
Highlights
Iron–sulfur clusters are ubiquitous in biology and function in electron transfer and catalysis
Due to the complex chemistry and energetic cost involved (ATP is used in initiating cluster release or recruiting Fe and cysteine must be regenerated), it is efficient for a cell to repair iron-sulfur clusters that become damaged by reactive oxygen or nitrogen species, and several repair systems have been proposed[4,5]
While the identity or need for a specific Fe donor for ironsulfur cluster biosynthesis is still under debate[6], Fe import and storage systems allow cells to avoid the toxicity of free ferrous iron in the presence of O2 while maintaining sufficient cellular iron in spite of the insolubility of free ferric iron at neutral pH7,8
Summary
Iron–sulfur clusters are ubiquitous in biology and function in electron transfer and catalysis They are assembled from iron and cysteine sulfur on protein scaffolds. The most common iron–sulfur cluster is the cubanetype [4Fe-4S] cluster, which is involved in electron transfer, catalysis, DNA repair and small molecule sensing[1] In spite of their high sensitivity to degradation by oxygen and reactive oxygen species, [4Fe-4S] clusters are ubiquitous in biology. To investigate the process of iron and sulfur storage and their incorporation into iron-sulfur clusters in an anaerobic microorganism that cannot use oxygen to oxidize ferrous iron, we examined the archaeon Pyrococcus furiosus, which grows optimally near 100 °C in hydrothermal marine vents[10] This strict anaerobe grows in the presence of elemental sulfur (S0) and uses it as an (insoluble) electron acceptor to generate (soluble) hydrogen sulfide[10]. P. furiosus does contain a homologue of the SufS cysteine desulfurase[1,2], but its natural hydrothermal vent environment is typically rich in sulfide and this could be directly incorporated into Fe–S clusters, which a 20 min b
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