A metal-trap tests and refines blueprints to engineer cellular protein metalation with different elements

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Jan. 18, 2025

It has been challenging to test how proteins acquire specific metals in cells. The speciation of metalation is thought depend on the preferences for different competing at intracellular metal-availabilities. This implies mis-metalation may occur if become mis-matched metal-availabilities heterologous Here we use a cyanobacterial MnII-cupin (MncA) as metal trap, predictions metalation. By re-folding MncA buffered metals, metal-preferences are determined. Relating estimated using cellular sensors, predicts with FeII E. coli. After expression coli, predominantly FeII-bound isolated experimentally. predicted that metal-supplemented viable cells metal-MncA should switch. MnII-, CoII-, or NiII-MncA recovered from respective Differences between observed and used refine availabilities. Values provided blueprints guide engineering biological protein

Language: Английский

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A dual absorption pathway of novel oyster-derived peptide-zinc complex enhances zinc bioavailability and restores mitochondrial function

Journal of Advanced Research, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

Zinc deficiency is a global health issue that impairs immune function, growth, and energy metabolism. Although conventional zinc supplements have been developed, their effectiveness limited by poor bioavailability susceptibility to dietary inhibitors. In this study, peptide-zinc complex (IE-Zn) derived from oysters was developed enhance uptake address metabolic disruptions caused deficiency. It determined Zn2+ binds with high affinity the IE peptide, promoting structural flexibility facilitates transport through both ion transporters oligopeptide transporters. Caco-2 IEC-6 cell models, IE-Zn shown significantly improve absorption retention compared ZnSO4, driven upregulation of ZIP4 PEPT1 vivo studies in zinc-deficient mouse model confirmed enhanced distribution across serum, intestine, liver. Moreover, restored homeostasis activating AMPK/PGC1-α/NRF-1/TFAM signaling pathway, mitochondrial biogenesis reducing oxidative stress. These findings suggest superior supplement higher serves as potent regulator cellular metabolism, offering therapeutic potential for managing conditions related dysfunction. This study lays foundation further exploration peptide-mineral complexes advanced nutritional broad applications. Subsequent will investigate pathway targeting complex. The hope provide preventive applications people need, including range diseases

Language: Английский

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Zng1 is a GTP-dependent zinc transferase needed for activation of methionine aminopeptidase

Cell Reports, Journal Year: 2022, Volume and Issue: 39(7), P. 110834 - 110834

Published: May 1, 2022

The evolution of zinc (Zn) as a protein cofactor altered the functional landscape biology, but dependency on Zn also created an Achilles' heel, necessitating adaptive mechanisms to ensure availability proteins. A debated strategy is whether metallochaperones exist prioritize essential Zn-dependent Here, we present evidence for conserved family putative metal transferases in human and fungi, which interact with methionine aminopeptidase type I (MetAP1/Map1p/Fma1). Deletion transferase Saccharomyces cerevisiae (ZNG1; formerly YNR029c) leads defective Map1p function Zn-deficiency growth defect. In vitro, Zng1p can transfer Zn2+ or Co2+ apo-Map1p, unlike characterized copper chaperones, dependent GTP hydrolysis. Proteomics reveal mis-regulation Zap1p transcription factor regulon because loss ZNG1 activity, suggesting that required avoid compounding effect dysfunction survival during limitation.

Language: Английский

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A model industrial workhorse: Bacillus subtilis strain 168 and its genome after a quarter of a century

Microbial Biotechnology, Journal Year: 2023, Volume and Issue: 16(6), P. 1203 - 1231

Published: April 1, 2023

Abstract The vast majority of genomic sequences are automatically annotated using various software programs. accuracy these annotations depends heavily on the very few manual annotation efforts that combine verified experimental data with from model organisms. Here, we summarize updated functional Bacillus subtilis strain 168, a quarter century after its genome sequence was first made public. Since last such effort 5 years ago, 1168 genetic functions have been updated, allowing construction new metabolic this organism environmental and industrial interest. emphasis in review is insights, role metals metabolism macromolecule biosynthesis, involved biofilm formation, features controlling cell growth, finally, protein agents allow class discrimination, thus maintenance management, all processes. New ‘genomic objects’ an extensive literature included for sequence, now available at International Nucleotide Sequence Database Collaboration (INSDC: AccNum AL009126.4).

Language: Английский

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A Systematic Study on Zinc-Related Metabolism in Breast Cancer

Nutrients, Journal Year: 2023, Volume and Issue: 15(7), P. 1703 - 1703

Published: March 31, 2023

Breast cancer has become the most common worldwide. Despite major advances made in past few decades treatment of breast using a combination chemotherapy, endocrine therapy, and immunotherapy, genesis, treatment, recurrence, metastasis this disease continue to pose significant difficulties. New approaches are therefore urgently required. Zinc is an important trace element that involved regulating various enzymatic, metabolic, cellular processes human body. Several studies have shown abnormal zinc homeostasis can lead onset progression diseases, including cancer. This review highlights role played by transporters pathogenesis, apoptosis, signal transduction, potential clinical applications Additionally, translation associated molecules cancer, as well recent developments zinc-related drug targets for discussed. These offer novel insights into understanding concepts could be used diagnosis management

Language: Английский

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Protein metalation in a nutshell

FEBS Letters, Journal Year: 2022, Volume and Issue: 597(1), P. 141 - 150

Published: Sept. 20, 2022

Metalation, the acquisition of metals by proteins, must avoid mis‐metalation with tighter binding metals. This is illustrated four selected proteins that require different metals: all show similar ranked orders affinity for bioavailable metals, as described in a universal series (the Irving–Williams series). Crucially, cellular protein metalation occurs competition other metal sites. The strength this defines intracellular availability each metal: its magnitude has been estimated calibrating cells' set DNA‐binding, metal‐sensing, transcriptional regulators. established availabilities (as free energies forming complexes) are maintained to inverse series. tightest least available. With these availabilities, correct achieved.

Language: Английский

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TerC proteins function during protein secretion to metalate exoenzymes

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Oct. 4, 2023

Cytosolic metalloenzymes acquire metals from buffered intracellular pools. How exported are appropriately metalated is less clear. We provide evidence that TerC family proteins function in metalation of enzymes during export through the general secretion (Sec-dependent) pathway. Bacillus subtilis strains lacking MeeF(YceF) and MeeY(YkoY) have a reduced capacity for protein greatly level manganese (Mn) secreted proteome. MeeF MeeY copurify with secretory pathway, their absence FtsH membrane protease essential viability. also required efficient Mn

Language: Английский

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Metal Homeostasis in Land Plants: A Perpetual Balancing Act Beyond the Fulfilment of Metalloproteome Cofactor Demands

Annual Review of Plant Biology, Journal Year: 2024, Volume and Issue: 75(1), P. 27 - 65

Published: Jan. 26, 2024

One of life's decisive innovations was to harness the catalytic power metals for cellular chemistry. With expansion, global atmospheric and biogeochemical cycles underwent dramatic changes. Although initially harmful, they permitted evolution multicellularity colonization land. In land plants as primary producers, metal homeostasis faces heightened demands, in part because soil is a challenging environment nutrient balancing. To avoid both limitation toxicity, must maintain within tighter limits than other minerals. This review describes present model protein metalation sketches its transfer from unicellular organisms complex multicellular organisms. The inseparable connection between redox increasingly draws our attention more general regulatory roles metals. Mineral co-option, use or functions nutrition, an emerging concept beyond that nutritional immunity.

Language: Английский

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Metals in Motion: Understanding Labile Metal Pools in Bacteria

Biochemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 5, 2025

Metal ions are essential for all life. In microbial cells, potassium (K+) is the most abundant cation and plays a key role in maintaining osmotic balance. Magnesium (Mg2+) dominant divalent required nucleic acid structure as an enzyme cofactor. Microbes typically require transition metals manganese (Mn), iron (Fe), copper (Cu), zinc (Zn), although precise set of metal needed to sustain life variable. Intracellular pools can be conceptualized chemically complex mixture rapidly exchanging (labile) ions, complemented by those reservoirs that exchange slowly relative cell metabolism (sequestered). Labile buffered transient interactions with anionic metabolites macromolecules, ribosome playing major role. Sequestered include many metalloproteins, cofactors, storage depots, some redeployed upon depletion. Here, I review size, composition, dynamics intracellular highlight gaps understanding.

Language: Английский

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Genomic analysis of surgical patients to identify patients at risk for postoperative sepsis and surgical site infection

Journal of Trauma and Acute Care Surgery, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 6, 2025

BACKGROUND Early and accurate diagnosis of sepsis the ensuing organ dysfunction remain a challenge in postoperative setting. Susceptibility to infections, as well subsequent immunological response, are driven some extent by genetic predisposition patient. The purpose this study was identify novel variants associated with (POS) surgical site infections (SSIs). METHODS We conducted genome-wide association studies for POS SSIs Electronic Medical Records Genomics Network database. All patients genomic information were identified. Patients new sepsis/SSIs after surgery classified cases, those without controls. Analyses performed using PLINK 2.0's logistic regression function. A p value <5 × 10 −8 considered statistically significant. RESULTS total 59,755 participants included analysis. Genetic regions on chromosomes 9 14 reached statistical significance ( < 5 ). most significant single-nucleotide polymorphisms (SNPs) rs9413988 = 5.59 −12 ) chromosome rs35407594 1.43 −10 14. region is downstream phosphoglucomutase pseudogene PGM5P2 Zn-regulated GTPase metalloprotein activator 1F ZNGF1 likely plays role transcription regulation, while corresponds olfactory receptor gene family, OR11 . Similar SNPs also SSIs. CONCLUSION have identified two containing These findings provide avenues investigation, which may help guide point-of-care management at-risk patients. LEVEL OF EVIDENCE Prognostic Epidemiological; Level III.

Language: Английский

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