Tyr25, Tyr58 and Trp133 of<i>Escherichia coli</i>bacterioferritin transfer electrons between iron in the central cavity and the ferroxidase centre

Bradley, Justin M.; Svistunenko, Dimitri A.; Moore, Geoffrey R.; Brun, Nick E. Le

doi:10.1039/c7mt00187h

Cited by 18 publications

(23 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Combining our observations with those of previous literature (Bradley et al, 2017b, Ebrahimi et al, 2013, Rui, Rivera et al, 2012, Turano et al, 2010, Yasmin et al, 2011), we propose the following mechanism to explain Fe trafficking in and out of the nanocage cavity (Fig 5). Fe 2+ ions enter through the B-pore and move into the ferroxidase center, where Fe 2+ is converted to Fe 3+ (Rui et al, 2012).…”

Section: Discussionsupporting

confidence: 86%

“…Although various pathways (Bradley et al, 2016, Bradley, Moore et al, 2017a, Bradley, Svistunenko et al, 2017b, Yao et al, 2012) have been proposed to explain the passage of iron in and out of the nanocage cavity, the exact mechanism remains unclear. In this context, our structures of the holo forms of the ScBfr nanocages reveal three intriguing features.…”

Section: Resultsmentioning

confidence: 99%

“…Indeed, mutating this conserved Lys42 to Ala (ScBfr K42A) reduces Fe binding as compared with the wild type (0.06 ppm vs. 0.27 ppm). Notably, in E. coli Bfr, Tyr34 has been reported to act as a molecular capacitor/electron donor for facilitating Fe oxidation (Bradley et al, 2017b, Ebrahimi, Hagedoorn et al, 2013) and Trp133 facilitates electron transfer (Bradley et al, 2017b). Collectively, these findings suggest that Tyr43 and Tyr133 in ScBfr might also contribute to electron transfer.…”

Section: Resultsmentioning

confidence: 99%

See 2 more Smart Citations

Cryo-EM Structure of Bacterioferritin Nanocages Provides Insight into the Bio-mineralization of Ferritins

Jobichen

Rattinam

et al. 2021

Preprint

View full text Add to dashboard Cite

Iron is an essential element involved in various metabolic processes. The ferritin family of proteins forms nanocage assembly and are involved in iron oxidation, storage and mineralization. Although several structures of human ferritin and bacterioferritin subunits have been resolved, there is still no complete structure that shows both the trapped Fe-biomineral cluster along with the nanocage. Furthermore, whereas the mechanism of iron trafficking has been explained using various approaches, an atomic-level description of the pathway and the biomineralization that occurs inside the cavity are lacking. Here, we report three cryo-EM structures of different states of the Streptomyces coelicolor bacterioferritin nanocage (i.e., apo, holo) at 3.4 Å to 4.6 Å resolution and the subunit crystal structure at 2.6 Å resolution. The holo forms show different stages of Fe-biomineral accumulation inside the nanocage and suggest the possibility of a different Fe biomineral accumulation process. The cryo-EM map shows connections between the Fe-biomineral cluster and residues such as Thr157 and Lys42 from the protein shell, which are involved in iron transport. Mutation and truncation of the bacterioferritin residues involved in these connections can significantly reduce iron binding as compared with wild type bacterioferritin. Moreover, S. coelicolor bacterioferritin binds to various DNA fragments, similar to Dps (DNA‐binding protein from starved cells) proteins. Collectively, our results represent a prototype for the ferritin nanocage, revealing insight into its biomineralization and the potential channel for ferritin-associated iron trafficking.

show abstract

Section: Discussionsupporting

confidence: 86%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Cryo-EM Structure of Bacterioferritin Nanocages Provides Insight into the Bio-mineralization of Ferritins

Jobichen

Rattinam

et al. 2021

Preprint

View full text Add to dashboard Cite

show abstract

“…Given the thickness of the protein shell (~2 nm), it is reasonable to assume that these electron transfer processes are not arbitrary, but rather a conserved evolutionary feature of ferritin, accompanied by specific protein structural arrangements. Interestingly, recent reports demonstrated the importance of electron transfer reactions, carried by three aromatic residues surrounding the diiron center of E. coli bacterial ferritin in the formation of the iron mineral core [54,55].…”

Section: Iron Mobilization By Reduced Flavinsmentioning

confidence: 99%

Reductive Mobilization of Iron from Intact Ferritin: Mechanisms and Physiological Implication

et al. 2018

View full text Add to dashboard Cite

Ferritins are highly conserved supramolecular protein nanostructures composed of two different subunit types, H (heavy) and L (light). The two subunits co-assemble into a 24-subunit heteropolymer, with tissue specific distributions, to form shell-like protein structures within which thousands of iron atoms are stored as a soluble inorganic ferric iron core. In-vitro (or in cell free systems), the mechanisms of iron(II) oxidation and formation of the mineral core have been extensively investigated, although it is still unclear how iron is loaded into the protein in-vivo. In contrast, there is a wide spread belief that the major pathway of iron mobilization from ferritin involves a lysosomal proteolytic degradation of ferritin, and the dissolution of the iron mineral core. However, it is still unclear whether other auxiliary iron mobilization mechanisms, involving physiological reducing agents and/or cellular reductases, contribute to the release of iron from ferritin. In vitro iron mobilization from ferritin can be achieved using different reducing agents, capable of easily reducing the ferritin iron core, to produce soluble ferrous ions that are subsequently chelated by strong iron(II)-chelating agents. Here, we review our current understanding of iron mobilization from ferritin by various reducing agents, and report on recent results from our laboratory, in support of a mechanism that involves a one-electron transfer through the protein shell to the iron mineral core. The physiological significance of the iron reductive mobilization from ferritin by the non-enzymatic FMN/NAD(P)H system is also discussed.

show abstract

“…Crystallographic studies identified an iron binding site, FeIS, located on the inner surface of the protein that is important for function (161). This, together with a network of aromatic residues, including the tyrosine conserved in other classes of ferritin (Tyr25 in this instance), deliver electrons into the ferroxidase center, generating Fe 3+ within the protein cage in the process (164,165). The reduced ferroxidase center then reacts with a further oxidizing equivalent completing the catalytic cycle.…”

Section: Iron Oxidation In Bfrsmentioning

confidence: 99%

Bacterial iron detoxification at the molecular level

Bradley

Svistunenko

Wilson

et al. 2020

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

Iron is an essential micro-nutrient and, in the case of bacteria, its availability is commonly a growth-limiting factor. However, correct functioning of cells requires that the labile pool of chelatable ‘free’ iron is tightly regulated. Correct metalation of proteins requiring iron as a cofactor demands that such a readily accessible source of iron exists, but over-accumulation results in an oxidative burden that, if unchecked, would lead to cell death. The toxicity of iron stems from its potential to catalyze formation of reactive oxygen species (ROS) that, in addition to causing damage to biological molecules, can also lead to the formation of reactive nitrogen species (RNS). In order to avoid iron-mediated oxidative stress, bacteria utilize iron-dependent global regulators to sense the iron status of the cell and regulate the expression of proteins involved in the acquisition, storage and efflux of iron accordingly. Here, we survey the current understanding of the structure and mechanism of the important members of each of these classes of protein. Diversity in the details of iron homeostasis mechanisms reflect the differing nutritional stresses resulting from the wide variety of ecological niches that bacteria inhabit. However, in this review we seek to highlight the similarities of iron homeostasis between different bacteria, whilst acknowledging important variations. In this way we hope to illustrate how bacteria have evolved common approaches to overcome the dual problems of the insolubility and potential toxicity of iron.

show abstract

Tyr25, Tyr58 and Trp133 ofEscherichia colibacterioferritin transfer electrons between iron in the central cavity and the ferroxidase centre

Cited by 18 publications

References 38 publications

Cryo-EM Structure of Bacterioferritin Nanocages Provides Insight into the Bio-mineralization of Ferritins

Cryo-EM Structure of Bacterioferritin Nanocages Provides Insight into the Bio-mineralization of Ferritins

Reductive Mobilization of Iron from Intact Ferritin: Mechanisms and Physiological Implication

Bacterial iron detoxification at the molecular level

Contact Info

Product

Resources

About