Prokaryotic Ferrous Iron Transport: Exploiting Pools of Reduced Iron Across Multiple Microbial Environments

Sestok, Alex E.; Lee, Mark A.; Smith, Aaron T.

doi:10.1007/978-3-030-97185-4_12

Cited by 3 publications

(3 citation statements)

References 167 publications

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“…However, subsequent studies of FeoB showed that the NFeoB domain from E. coli was GTP-specific (41), and structures of NFeoB from Methanocaldococcus jannaschii and E. coli revealed the presence of a G-protein like domain (34,42), strongly implying that NFeoB bound and hydrolyzed only guanine nucleotides. This presumption continued for nearly two additional decades, as additional NFeoB structures were determined and FeoB was further explored in an almost GTPexclusive manner (12,14,18). However, despite this assumption, Shin et al reexamined NTPase activity in the context of V. cholerae FeoB and found this protein to be nucleotide promiscuous both in vitro and in vivo (24).…”

Section: Discussionmentioning

confidence: 99%

“…7-10 kDa) cytosolic proteins, while FeoB is a large ( ca . 80-100 kDa) polytopic transmembrane protein that contains an N-terminal soluble G-protein-like domain termed NFeoB(12, 14, 18). The roles of FeoA and FeoC remain somewhat enigmatic; however, these proteins have been shown to interact with NFeoB in vitro(19) , FeoA appears to regulate GTP hydrolysis in vitro(17) , and some FeoCs bind oxygen-sensitive [Fe-S] clusters, presumably for regulatory purposes(20).…”

Section: Introductionmentioning

confidence: 99%

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Structural Determinants ofVibrio choleraeFeoB Nucleotide Promiscuity

Lee,

Magante,

Gómez-Garzón

et al. 2024

Preprint

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Ferrous iron (Fe2+) is required for the growth and virulence of many pathogenic bacteria, includingVibrio cholerae(Vc), the causative agent of the disease cholera. For this bacterium, Feo is the primary system that transports Fe2+into the cytosol. FeoB, the main component of this system, is regulated by a soluble cytosolic domain termed NFeoB. Recent reanalysis has shown that NFeoBs can be classified as either GTP-specific or NTP-promiscuous, but the structural and mechanistic bases for these differences were not known. To explore this intriguing property of FeoB, we solved the X-ray crystal structures ofVcNFeoB in both the apo and GDP-bound forms. Surprisingly, this promiscuous NTPase displayed a canonical NFeoB G-protein fold like GTP-specific NFeoBs. Using structural bioinformatics, we hypothesized that residues surrounding the nucleobase could be important for both nucleotide affinity and specificity. We then solved the X-ray crystal structures of N150TVcNFeoB in the apo and GDP-bound forms to reveal H-bonding differences surround the guanine nucleobase. Interestingly, isothermal titration calorimetry revealed similar binding thermodynamics of the WT and N150T proteins to guanine nucleotides, while the behavior in the presence of adenine nucleotides was dramatically different. AlphaFold models ofVcNFeoB in the presence of ADP and ATP showed important conformational changes that contribute to nucleotide specificity among FeoBs. Combined, these results provide a structural framework for understanding FeoB nucleotide promiscuity, which could be an adaptive measure utilized by pathogens to ensure adequate levels of intracellular iron across multiple metabolic landscapes.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Structural Determinants ofVibrio choleraeFeoB Nucleotide Promiscuity

Lee,

Magante,

Gómez-Garzón

et al. 2024

Preprint

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“…Iron (Fe) is the most abundant transition metal on earth and is an essential nutrient for almost all organisms due to its participation in critical cellular and metabolic processes, such as deoxyribonucleic acid (DNA) biosynthesis, cellular respiration, amino acid biosynthesis, electron transport, O 2 transport, and even N 2 fixation. − This impressive range of activity is due to the versatility of Fe as a cofactor. For example, Fe can span multiple oxidation states, such as ferrous (Fe 2+ ), ferric (Fe 3+ ), and ferryl (Fe 4+ ), can accommodate several coordination states, and its redox potential can span nearly a 1 V range .…”

Section: Iron Sensing Two-component Systemsmentioning

confidence: 99%

Metal Messengers: Communication in the Bacterial World through Transition-Metal-Sensing Two-Component Systems

Paredes,

Iheacho,

Smith

2023

Biochemistry

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Bacteria survive in highly dynamic and complex environments due, in part, to the presence of systems that allow the rapid control of gene expression in the presence of changing environmental stimuli. The crosstalk between intra-and extracellular bacterial environments is often facilitated by two-component signal transduction systems that are typically composed of a transmembrane histidine kinase and a cytosolic response regulator. Sensor histidine kinases and response regulators work in tandem with their modular domains containing highly conserved structural features to control a diverse array of genes that respond to changing environments. Bacterial two-component systems are widespread and play crucial roles in many important processes, such as motility, virulence, chemotaxis, and even transition metal homeostasis. Transition metals are essential for normal prokaryotic physiological processes, and the presence of these metal ions may also influence pathogenic virulence if their levels are appropriately controlled. To do so, bacteria use transition-metal-sensing two-component systems that bind and respond to rapid fluctuations in extracytosolic concentrations of transition metals. This perspective summarizes the structural and metal-binding features of bacterial transition-metal-sensing two-component systems and places a special emphasis on understanding how these systems are used by pathogens to establish infection in host cells and how these systems may be targeted for future therapeutic developments.

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