Structural model of FeoB, the iron transporter from<i>Pseudomonas aeruginosa</i>, predicts a cysteine lined, GTP-gated pore

Seyedmohammad, Saeed; Fuentealba, Natalia Alveal; Marriott, Robert A.J.; Goetze, Tom A.; Edwardson, J. Michael; Barrera, Nelson P.; Venter, Henrietta

doi:10.1042/bsr20160046

Cited by 34 publications

(30 citation statements)

References 73 publications

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“…4 H). Also, a recent atomic force microscopy study on FeoB from Pseudomonas aeruginosa revealed a large amount of monomers in FeoB samples, whereas peaks interpreted as trimers and hexamers were found to a smaller extent (38). Taken together, it appears that both NFeoB and full-length FeoB are mostly monomeric in solution, while oligomers are formed to a small extent.…”

Section: Discussionmentioning

confidence: 92%

Studies on the X-Ray and Solution Structure of FeoB from Escherichia coli BL21

Hagelueken

Hoffmann

Schubert

et al. 2016

Biophysical Journal

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The ferrous iron transporter FeoB is an important factor in the iron metabolism of many bacteria. Although several structural studies have been performed on its cytosolic GTPase domain (NFeoB), the full-length structure of FeoB remains elusive. Based on a crystal packing analysis that was performed on crystals of NFeoB, a trimeric structure of the FeoB channel was proposed, where the transport pore runs along the trimer axis. Because this trimer has not been observed in some subsequently solved structures of NFeoB homologs, it remains unclear whether or not the trimer is indeed functionally relevant. Here, pulsed electron-electron double resonance spectroscopy, negative stain electron microscopy, and native mass spectrometry are used to analyze the oligomeric state of different soluble and full-length FeoB constructs. The results show that the full-length protein is predominantly monomeric, whereas dimers and trimers are formed to a small percentage. Furthermore, the solution structure of the switch I region is analyzed by pulsed electron-electron double resonance spectroscopy and a new, to our knowledge, crystal structure of NFeoB from Escherichia coli BL21 is presented.

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Section: Discussionmentioning

confidence: 92%

Studies on the X-Ray and Solution Structure of FeoB from Escherichia coli BL21

Hagelueken

Hoffmann

Schubert

et al. 2016

Biophysical Journal

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“…Another group reported the 9-cisRA showed a prominent decrease from normal controls with localized BC to metastatic BC based on the analysis of 46 clinical serum and urine samples 58. Oestrogen was regarded as a dual effector of BC 59. Lysophosphatidylcholines and phosphatidylcholines were found to be significantly elevated in the oestrogen-induced group after comparing the serum metabolites profiles of an oestrogen-induced BC model with those of the control group through ultra-high performance liquid chromatography (UHPLC)-time-of-flight tandem mass spectrometer (QTOF-MS/MS) 60.…”

Section: The Application Of Metabolomics In the Clinical Practice Of Bcmentioning

confidence: 99%

<p>Metabolomics: a promising diagnostic and therapeutic implement for breast cancer</p>

Chen¹,

Li²,

Li³

et al. 2019

OTT

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Breast cancer (BC) is the most commonly diagnosed cancer among women and the leading cause of cancer death. Despite the advent of numerous diagnosis and treatment methods in recent years, this heterogeneous disease still presents great challenges in early diagnosis, curative treatments and prognosis monitoring. Thus, finding promising early diagnostic biomarkers and therapeutic targets and approaches is meaningful. Metabolomics, which focuses on the analysis of metabolites that change during metabolism, can reveal even a subtle abnormal change in an individual. In recent decades, the exploration of cancer-related metabolomics has increased. Metabolites can be promising biomarkers for the screening, response evaluation and prognosis of BC. In this review, we summarized the workflow of metabolomics, described metabolite signatures based on molecular subtype as well as reclassification and then discussed the application of metabolomics in the early diagnosis, monitoring and prognosis of BC to offer new insights for clinicians in breast cancer diagnosis and treatment.

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“…Three SNPs were identified in the Δdpr-B genome (stress-tolerant, rough colony), all within the smu995 coding region, including a cysteine-to-serine substitution (C¡S) at residue 66, a glycine to serine substitution (G¡S) at residue 67 and a glycine-to-valine substitution (G¡V) also at residue 67. While any one of these amino acid substitutions may have potentially affected Smu995 function, the replacement of the cysteine residue by serine is the most likely to impair protein function given that conserved cysteine residues are critical for the function of iron transport proteins of Klebsiella pneumoniae and Pseudomonas aeruginosa (24,25). Finally, four SNPs were identified in the Δdpr-C isolate (stress-tolerant, smooth colony).…”

Section: Resultsmentioning

confidence: 99%

Disruption of a Novel Iron Transport System Reverses Oxidative Stress Phenotypes of a dpr Mutant Strain of Streptococcus mutans

et al. 2018

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The Dps-like peroxide resistance protein (Dpr) is essential for HO stress tolerance and aerobic growth of the oral pathogen Dpr accumulates during oxidative stress, protecting the cell by sequestering iron ions and thereby preventing the generation of toxic hydroxyl radicals that result from the interaction of iron with HO Previously, we reported that the SpxA1 and SpxA2 regulators positively regulate expression of in Using an antibody raised against Dpr, we confirmed at the protein level the central and cooperative nature of SpxA1 and SpxA2 regulation in Dpr production. During phenotypic characterization of the Δ strain, we observed the appearance of distinct colony variants, which sometimes lost the oxidative stress sensitivity typical of Δ strains. Whole-genome sequencing of these phenotypically distinct Δ isolates revealed that a putative iron transporter operon, , was a genomic hot spot with multiple single nucleotide polymorphisms identified within the different isolates. Deletion of or the entire operon in the Δ background strain completely reversed the oxidative stress-sensitive phenotypes associated with inactivation. Conversely, inactivation of genes encoding the ferrous iron transport system FeoABC did not alleviate phenotypes of the Δ strain. Preliminary characterization of strains lacking ,, and the iron/manganese transporter gene revealed the interactive nature of these three systems in iron transport but also indicated that there may be additional iron uptake systems in The dental caries-associated pathogen routinely encounters oxidative stress within the human plaque biofilm. Previous studies revealed that the iron-binding protein Dpr confers protection toward oxidative stress by limiting free iron availability, which is associated with the generation of toxic hydroxyl radicals. Here, we report the identification of spontaneously occurring mutations within Δ strains. Several of those mutations were mapped to the operon , revealing a previously uncharacterized system that appears to be important in iron acquisition. Disruption of the operon resulted in reversion of the stress-sensitive phenotype typical of a Δ strain. Our data suggest that the Smu995-Smu998 system works along with other known metal transport systems of , i.e., FeoABC and SloABC, to coordinate iron uptake.

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Structural model of FeoB, the iron transporter fromPseudomonas aeruginosa, predicts a cysteine lined, GTP-gated pore

Abstract: The bacterial ferrous iron acquisition protein FeoB assembles as a homotrimer that is predicted to form a central pore lined by conserved cysteine residues. Structure-function analysis of FeoB indicates a putative mechanism more akin to a GTP-gated channel than a transporter.

Cited by 34 publications

References 73 publications

Studies on the X-Ray and Solution Structure of FeoB from Escherichia coli BL21

Studies on the X-Ray and Solution Structure of FeoB from Escherichia coli BL21

<p>Metabolomics: a promising diagnostic and therapeutic implement for breast cancer</p>

Disruption of a Novel Iron Transport System Reverses Oxidative Stress Phenotypes of a dpr Mutant Strain of Streptococcus mutans

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