共查询到20条相似文献,搜索用时 15 毫秒
1.
Emilia Chiancone Pierpaolo Ceci Andrea Ilari Frederica Ribacchi Simonetta Stefanini 《Biometals》2004,17(3):197-202
Iron is required by most organisms, but is potentially toxic due to the low solubility of the stable oxidation state, Fe(III), and to the tendency to potentiate the production of reactive oxygen species, ROS. The reactivity of iron is counteracted by bacteria with the same strategies employed by the host, namely by sequestering the metal into ferritin, the ubiquitous iron storage protein. Ferritins are highly conserved, hollow spheres constructed from 24 subunits that are endowed with ferroxidase activity and can harbour up to 4500 iron atoms as oxy-hydroxide micelles. The release of the metal upon reduction can alter the microorganism-host iron balance and hence permit bacteria to overcome iron limitation. In bacteria, the relevance of the Dps (DNA-binding proteins from starved cells) family in iron storage-detoxification has been recognized recently. The seminal studies on the protein from Listeria innocua demonstrated that Dps proteins have ferritin-like activity and most importantly have the capacity to attenuate the production of ROS. This latter function allows bacterial pathogens that lack catalase, e.g. Porphyromonas gingivalis, to survive in an aerobic environment and resist to peroxide stress. 相似文献
2.
Background
The widely expressed Dps proteins, so named after the DNA-binding properties of the first characterized member of the family in Escherichia coli, are considered major players in the bacterial response to stress.Scope of review
The review describes the distinctive features of the “ferritin-like” ferroxidation reaction, which uses hydrogen peroxide as physiological iron oxidant and therefore permits the concomitant removal of the two reactants that give rise to hydroxyl radicals via Fenton chemistry. It also illustrates the structural elements identified to date that render the interaction of some Dps proteins with DNA possible and outlines briefly the significance of Dps–DNA complex formation and of the Dps interaction with other DNA-binding proteins in relation to the organization of the nucleoid and microbial survival.General significance
Understanding in molecular terms the distinctive role of Dps proteins in bacterial resistance to general and specific stress conditions.Major conclusions
The state of the art is that the response to oxidative and peroxide-mediated stress is mediated directly by Dps proteins via their ferritin-like activity. In contrast, the response to other stress conditions derives from the concerted interplay of diverse interactions that Dps proteins may establish with DNA and with other DNA-binding proteins. 相似文献3.
Roy S Saraswathi R Gupta S Sekar K Chatterji D Vijayan M 《Journal of molecular biology》2007,370(4):752-767
Mycobacterium smegmatis Dps degrades spontaneously into a species in which 16 C-terminal residues are cleaved away. A second species, in which all 26 residues constituting the tail were deleted, was cloned, expressed and purified. The first did not bind DNA but formed dodecamers like the native protein, while the second did not bind to DNA and failed to assemble into dodecamers, indicating a role in assembly also for the tail. In the crystal structure of the species without the entire C-terminal tail the molecule has an unusual open decameric structure resulting from the removal of two adjacent subunits from the original dodecameric structure of the native form. A Dps dodecamer could assemble with a dimer or one of two trimers (trimer-A and trimer-B) as intermediate. Trimer-A is the intermediate species in the M. smegmatis protein. Estimation of the surface area buried on trimerization indicates that association within trimer-B is weak. It weakens further when the C-terminal tail is removed, leading to the disruption of the dodecameric structure. Thus, the C-terminal tail has a dual role, one in DNA binding and the other in the assembly of the dodecamer. M. smegmatis Dps also has a short N-terminal tail. A species with nine N-terminal residues deleted formed trimers but not dodecamers in solution, unlike wild-type M. smegmatis Dps, under the same conditions. Unlike in solution, the N-terminal mutant forms dodecamers in the crystal. In native Dps, the N-terminal stretch of one subunit and the C-terminal stretch of a neighboring subunit lock each other into ordered positions. The deletion of one stretch results in the disorder of the other. This disorder appears to result in the formation of a trimeric species of the N-terminal deletion mutant contrary to the indication provided by the native structure. The ferroxidation site is intact in the mutants. 相似文献
4.
A second DNA binding protein from stationary-phase cells of Mycobacterium smegmatis (MsDps2) has been identified from the bacterial genome. It was cloned, expressed and characterised and its crystal structure was determined. The core dodecameric structure of MsDps2 is the same as that of the Dps from the organism described earlier (MsDps1). However, MsDps2 possesses a long N-terminal tail instead of the C-terminal tail in MsDps1. This tail appears to be involved in DNA binding. It is also intimately involved in stabilizing the dodecamer. Partly on account of this factor, MsDps2 assembles straightway into the dodecamer, while MsDps1 does so on incubation after going through an intermediate trimeric stage. The ferroxidation centre is similar in the two proteins, while the pores leading to it exhibit some difference. The mode of sequestration of DNA in the crystalline array of molecules, as evidenced by the crystal structures, appears to be different in MsDps1 and MsDps2, highlighting the variability in the mode of Dps-DNA complexation. A sequence search led to the identification of 300 Dps molecules in bacteria with known genome sequences. Fifty bacteria contain two or more types of Dps molecules each, while 195 contain only one type. Some bacteria, notably some pathogenic ones, do not contain Dps. A sequence signature for Dps could also be derived from the analysis. 相似文献
5.
Mathew Stracy Jakob Schweizer David J. Sherratt Achillefs N. Kapanidis Stephan Uphoff Christian Lesterlin 《Molecular cell》2021,81(7):1499-1514.e6
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6.
The ferritin-like DNA-binding protein from starved cells (Dps) family proteins are present in a number of pathogenic bacteria. Dps in the enterohepatic pathogen, Helicobacter hepaticus is characterized and a H. hepaticus dps mutant was generated by insertional mutagenesis. While the wild type H. hepaticus cells were able to survive in an atmosphere containing up to 6.0% O2, the dps mutant failed to grow in 3.0% O2, and it was also more sensitive to oxidative reagents like H2O2, cumene hydroperoxide and t-butyl hydroperoxide. Upon air exposure, the dps- cells had more damaged DNA than the wild type; they became coccoid or lysed and they contained ∼6-fold higher amount of 8-oxoguanine (8-oxoG) DNA lesions than wild type cells. Purified H. hepaticus Dps was shown to be able to bind both iron and DNA. The iron-loaded form of Dps protein had much greater DNA binding ability than the native Dps or the iron-free Dps. 相似文献
7.
Holm PJ Bhakat P Jegerschöld C Gyobu N Mitsuoka K Fujiyoshi Y Morgenstern R Hebert H 《Journal of molecular biology》2006,360(5):934-945
Synthesis of mediators of fever, pain and inflammation as well as protection against reactive molecules and oxidative stress is a hallmark of the MAPEG superfamily (membrane associated proteins in eicosanoid and glutathione metabolism). The structure of a MAPEG member, rat microsomal glutathione transferase 1, at 3.2 A resolution, solved here in complex with glutathione by electron crystallography, defines the active site location and a cytosolic domain involved in enzyme activation. The glutathione binding site is found to be different from that of the canonical soluble glutathione transferases. The architecture of the homotrimer supports a catalytic mechanism involving subunit interactions and reveals both cytosolic and membraneous substrate entry sites, providing a rationale for the membrane location of the enzyme. 相似文献
8.
The structure of chromatin is the major factor determining the rate and efficiency of DNA repair. Chromatin remodeling events
such as rearrangement of nucleosomes and higher order chromatin structures are indispensable features of repair processes.
During the last decade numerous chromatin proteins have been identified that preferentially bind to different types of DNA
damage. The HMGB proteins, which preferentially interact with DNA intrastrand crosslinks induced by cisplatin, are the archetypal
example of such proteins. Several hypothetical models have been proposed describing the role of such damage-binding chromatin
proteins. The damage shielding model postulates that binding of chromatin proteins to damaged DNA might disturb damage recognition
by repair factors and impair its removal. Alternatively, the damage-recognition/signaling model proposes that the binding
of specific chromatin proteins to damaged DNA could serve as a hallmark to be recognized by repair proteins. Additionally,
the binding of specific chromatin proteins to damaged DNA could induce chromatin remodeling at the damage site and indirectly
affect its repair. This paper aims to critically review current experimental data in relation to such possible roles of chromatin
proteins. 相似文献
9.
Bacterial iron storage proteins such as ferritin serve as intracellular iron reserves. Members of the DNA protection during starvation (Dps) family of proteins are structurally related to ferritins, and their function is to protect the genome from iron-induced free radical damage. Some members of the Dps family bind DNA and are thought to do so only as fully assembled dodecamers. We present the cloning and characterization of a Dps homolog encoded by the radiation-resistant eubacterium Deinococcus radiodurans and show that DNA binding does not require its assembly into a dodecamer. D.radiodurans Dps-1, the product of gene DR2263, adopts a stably folded conformation, as demonstrated by circular dichroism spectroscopy, and undergoes a transition to a disordered state with a melting temperature of 69.2(+/-0.1) degrees C. While a dimeric form of Dps-1 is observed under low-salt conditions, a dodecameric assembly is highly favored at higher concentrations of salt. Both oligomeric forms of Dps-1 exhibit ferroxidase activity, and Fe(II) oxidation/mineralization is seen for dodecameric Dps-1. Notably, addition of Ca(2+) (to millimolar concentrations) to dodecameric Dps-1 can result in the reduction of bound Fe(III). Dimeric Dps-1 protects DNA from both hydroxyl radical cleavage and from DNase I-mediated cleavage; however, dodecameric Dps-1 is unable to provide efficient protection against hydroxyl radical-mediated DNA cleavage. While dodecameric Dps-1 does bind DNA, resulting in formation of large aggregates, cooperative DNA binding by dimeric Dps-1 leads to formation of protein-DNA complexes of finite stoichiometry. 相似文献
10.
DnaJ, DjlA and CbpA are the J-domain proteins of DnaK, the major Hsp70 of Escherichia coli. CbpA was originally discovered as a DNA binding protein. Here, we show that DNA binding is a property of DnaJ and DjlA as well. Of special interest in this respect is DjlA, as this cytoplasmic protein is membrane bound and, as shown here, its affinity for DNA is extremely high. The finding that all the three J-proteins of DnaK are DNA binding proteins sheds new light on the cellular activity of these proteins. 相似文献
11.
Oxidative stress is an unavoidable byproduct of aerobic life. Molecular oxygen is essential for terrestrial metabolism, but it also takes part in many damaging reactions within living organisms. The combination of aerobic metabolism and iron, which is another vital compound for life, is enough to produce radicals through Fenton chemistry and degrade cellular components. DNA degradation is arguably the most damaging process involving intracellular radicals, as DNA repair is far from trivial. The assay presented in this article offers a quantitative technique to measure and visualize the effect of molecules and enzymes on radical-mediated DNA damage.The DNA protection assay is a simple, quick, and robust tool for the in vitro characterization of the protective properties of proteins or chemicals. It involves exposing DNA to a damaging oxidative reaction and adding varying concentrations of the compound of interest. The reduction or increase of DNA damage as a function of compound concentration is then visualized using gel electrophoresis. In this article we demonstrate the technique of the DNA protection assay by measuring the protective properties of the DNA-binding protein from starved cells (Dps). Dps is a mini-ferritin that is utilized by more than 300 bacterial species to powerfully combat environmental stressors. Here we present the Dps purification protocol and the optimized assay conditions for evaluating DNA protection by Dps. 相似文献
12.
Rowan A. Grayling Kathryn A. Bailey John N. Reeve 《Extremophiles : life under extreme conditions》1997,1(2):79-88
The DNA-binding and nuclease-protection properties of the HMf histones from the hyperthermophilic archaeon Methanothermus fervidus have been shown to be consistent with the formation of nucleosome-like structures (NLS). These proteins bind to DNA molecules
as short as 20 bp and form complexes that protect DNA fragments from micrococcal nuclease (MNase) digestion that are 30 bp,
∼ 60 bp and multiples of ∼ 60 bp in length. The sequences of 49 of the ∼ 60-bp DNA fragments protected from MNase digestion
by HMfA have been determined and their intrinsic curvatures calculated. A circular permutation gel mobility-shift assay was
used to determine directly the curvatures for five of these sequences. HMfA bound to intrinsically curved and noncurved DNAs,
but exhibited a slight preference for the model curved DNA in binding competitions with a model noncurved DNA. The results
obtained are consistent with the concept that the archaeal NLS is analogous, and possibly homologous, to the central core
of the eukaryal nucleosome formed by a histone (H3 + H4)2 tetramer.
Received: August 11, 1996 / Accepted: November 12, 1996 相似文献
13.
Activity of chloroplast-localized DNA endonuclease was observed in detached tobacco leaves that had been treated with paraquat
and light The DNA endonuclease was able to cleave the chloroplast, plasmid, and single-stranded DNA, as estimated on an agarose
gel. Activity was sensitive to two endonuclease inhibitors: aurintricarboxylic acid and ZnSO4. The time course for activity showed a peak 4 h after the stress treatment These results suggest that this enzyme plays a
specific physiological role during oxidative stress. Probable roles for this enzyme are also discussed. 相似文献
14.
Francesco Fazio Stefania Casella Claudia Giannetto Elisabetta Giudice Giuseppe Piccione 《Experimental Animals》2015,64(1):19-24
Haptoglobin (Hp), serum amyloid A (SAA), C-reactive protein (CRP), white blood cells
(WBC), reactive oxygen metabolites (ROMs), the antioxidant barrier (Oxy-adsorbent) and
thiol groups of plasma compounds (SHp) were measured in ten dogs that had been transported
a distance of about 230 km within 2 h (experimental group) and in ten dogs that had not
been subjected to road transportation (control group). Blood was collected via cephalic
venipuncture before road transportation (T0), after road transportation (T1), and more
than 6 (T6) and 24 (T24) hours after road transportation in the experimental group (Group
A) and at the same time points in the control group (Group B). The GLM (general linear
model) Repeated Measures procedure showed a significant difference between the two groups
(P<0.0001) and a significant rise (P<0.0001) in
the concentrations of Hp, SAA, CRP, WBC, ROMs, Oxy-adsorbent and SHp after road
transportation in Group A, underlining that physiological and homeostatic mechanisms are
modified differently at various sampling times. 相似文献
15.
The Dps family of proteins are a diverse group of bacterial stress-inducible polypeptides that bind DNA and likely confer resistance to peroxide damage during periods of oxidative stress and long-term nutrient limitation. Some members of the Dps protein family have been shown to form abundant, large (∼150 kD) hexameric complexes that bind chromosomal DNA with little sequence specificity. Previous work from this lab has demonstrated that the Dps proteins are divergent members of the bacterioferritin/bacterioferritin superfamily, and that the Synechococcus sp. PCC7942 Dps homolog, named DpsA, is a DNA-binding hemoprotein having heme-dependent catalytic activity. We speculated that this protein may yield a peroxide-consuming mechanism located on the chromosomal DNA, and we also suggested that this activity may be a necessary feature to handle the endogenous oxidative stresses associated with oxygenic photosynthesis. Current work has examined the expression of dpsA both under nutrient stress and during the growth phase; whereas dpsA mRNA is detectable in the exponential phase, transition to stationary phase yields a 20-fold increase in steady-state mRNA levels. Mapping the promoter region identifies a TAGAAT −10 sequence likely recognized by a cyanobacterial RpoS homolog. Lastly, site-directed mutants lacking dpsA function exhibit a severe phenotype impaired under all conditions yielding photooxidative stress; these include high light and treatment with paraquat. This supports our contention that the DpsA protein serves an important protective function in an obligate photoautotroph. 相似文献
16.
Setareh Rezatabar Ansar Karimian Vahid Rameshknia Hadi Parsian Maryam Majidinia Tayebeh Azramezani Kopi Anupam Bishayee Ali Sadeghinia Mehdi Yousefi Mohsen Monirialamdari Bahman Yousefi 《Journal of cellular physiology》2019,234(9):14951-14965
Mitogen-activated protein kinase (MAPK) signaling pathways organize a great constitution network that regulates several physiological processes, like cell growth, differentiation, and apoptotic cell death. Due to the crucial importance of this signaling pathway, dysregulation of the MAPK signaling cascades is involved in the pathogenesis of various human cancer types. Oxidative stress and DNA damage are two important factors which in common lead to carcinogenesis through dysregulation of this signaling pathway. Reactive oxygen species (ROS) are a common subproduct of oxidative energy metabolism and are considered to be a significant physiological modulator of several intracellular signaling pathways including the MAPK pathway. Studies demonstrated that the MAP kinases extracellular signal-regulated kinase (ERK) 1/2 and p38 were activated in response to oxidative stress. In addition, DNA damage is a partly common circumstance in cell life and may result in mutation, cancer, and even cell death. Recently, accumulating evidence illustrated that the MEK/ERK pathway is associated with the suitable performance of cellular DNA damage response (DDR), the main pathway of tumor suppression. During DDR, the MEK/ERK pathway is regularly activated, which contributes to the appropriate activation of DDR checkpoints to inhibit cell division. Therefore, the aim of this review is to comprehensively discuss the critical function of MAPK signaling in oxidative stress, DNA damage, and cancer progression. 相似文献
17.
Alessandri M Beretta GL Ferretti E Mancia A Khobta A Capranico G 《Journal of molecular biology》2004,337(2):295-305
Human topoisomerase I-B (Top1) efficiently relaxes DNA supercoils during basic cellular processes, and can be transformed into a DNA-damaging agent by antitumour drugs, enzyme mutations and DNA lesions. Here, we describe Gal4-Top1 chimeric proteins (GalTop) with an N-terminal truncation of Top1, and mutations of the Gal4 Zn-cluster and/or Top1 domains that impair their respective DNA-binding activities. Expression levels of chimeras were similar in yeast cells, however, GalTop conferred an increased CPT sensitivity to RAD52- yeast cells as compared to a GalTop with mutations of the Gal4 domain, showing that a functional Gal4 domain can alter in vivo functions of Top1. In vitro enzyme activity was tested with a DNA relaxation assay using negatively supercoiled plasmids with 0 to 5 Gal4 consensus motifs. Only GalTop with a functional Gal4 domain could direct DNA relaxation activity of Top1 specifically to DNA molecules containing Gal4 motifs. By using a substrate competition assay, we could demonstrate that the Gal4-anchored Top1 remains functional and efficiently relax DNA substrates in cis. The enhanced CPT sensitivity of GalTop in yeast cells may then be due to alterations of the chromatin-binding activity of Top1. The GalTop chimeras may indeed mimic a normal mechanism by which Top1 is recruited to chromatin sites in living cells. Such hybrid Top1s may be helpful in further dissecting enzyme functions, and constitute a prototype of a site-specific DNA cutter endowed with high cell lethality. 相似文献
18.
Yibo Li Surya Amarachintha Andrew F. Wilson Xue Li 《Cell cycle (Georgetown, Tex.)》2017,16(12):1201-1209
Oxidative stress is considered as an important pathogenic factor in many human diseases including Fanconi anemia (FA), an inherited bone marrow failure syndrome with extremely high risk of leukemic transformation. Members of the FA protein family are involved in DNA damage and other cellular stress responses. Loss of FA proteins renders cells hypersensitive to oxidative stress and cancer transformation. However, how FA cells respond to oxidative DNA damage remains unclear. By using an in vivo stress-response mouse strain expressing the Gadd45β-luciferase transgene, we show here that haematopoietic stem and progenitor cells (HSPCs) from mice deficient for the FA gene Fanca or Fancc persistently responded to oxidative stress. Mechanistically, we demonstrated that accumulation of unrepaired DNA damage, particularly in oxidative damage-sensitive genes, was responsible for the long-lasting response in FA HSPCs. Furthermore, genetic correction of Fanca deficiency almost completely abolished the persistent oxidative stress-induced G2/M arrest and DNA damage response in vivo. Our study suggests that FA pathway is an integral part of a versatile cellular mechanism by which HSPCs respond to oxidative stress. 相似文献
19.
The crosstalk between trace elements with DNA damage response,repair, and oxidative stress in cancer
Sadra Samavarchi Tehrani Hamideh Mahmoodzadeh Hosseini Tooba Yousefi Maryam Abolghasemi Durdi Qujeq Mahmood Maniati Jafar Amani 《Journal of cellular biochemistry》2019,120(2):1080-1105
DNA damage response (DDR) is a regulatory system responsible for maintaining genome integrity and stability, which can sense and transduce DNA damage signals. The severity of damage appears to determine DDRs, which can include damage repair, cell-cycle arrest, and apoptosis. Furthermore, defective components in DNA damage and repair machinery are an underlying cause for the development and progression of various types of cancers. Increasing evidence indicates that there is an association between trace elements and DDR/repair mechanisms. In fact, trace elements seem to affect mediators of DDR. Besides, it has been revealed that oxidative stress (OS) and trace elements are associated with cancer development. In this review, we discuss the role of some critical trace elements in the risk of cancer. In addition, we provide a brief introduction on DDR and OS in cancer. Finally, we will further review the interactions between some important trace elements including selenium, zinc, chromium, cadmium, and arsenic, and DDR, and OS in cancer. 相似文献