Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

DsbA is a redox-switchable mechanical chaperone.

ABSTRACT: DsbA is a ubiquitous bacterial oxidoreductase that associates with substrates during and after translocation, yet its involvement in protein folding and translocation remains an open question. Here we demonstrate a redox-controlled chaperone activity of DsbA, on both cysteine-containing and cysteine-free substrates, using magnetic tweezers-based single molecule force spectroscopy that enables independent measurements of oxidoreductase activity and chaperone behavior. Interestingly we found that this chaperone activity is tuned by the oxidation state of DsbA; oxidized DsbA is a strong promoter of folding, but the effect is weakened by the reduction of the catalytic CXXC motif. We further localize the chaperone binding site of DsbA using a seven-residue peptide which effectively blocks the chaperone activity. We found that the DsbA assisted folding of proteins in the periplasm generates enough mechanical work to decrease the ATP consumption needed for periplasmic translocation by up to 33%.

SUBMITTER: Eckels EC

PROVIDER: S-EPMC8386657 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

DsbA is a redox-switchable mechanical chaperone.

Eckels Edward C EC Chaudhuri Deep D Chakraborty Soham S Echelman Daniel J DJ Haldar Shubhasis S

Chemical science 20210719 33

DsbA is a ubiquitous bacterial oxidoreductase that associates with substrates during and after translocation, yet its involvement in protein folding and translocation remains an open question. Here we demonstrate a redox-controlled chaperone activity of DsbA, on both cysteine-containing and cysteine-free substrates, using magnetic tweezers-based single molecule force spectroscopy that enables independent measurements of oxidoreductase activity and chaperone behavior. Interestingly we found that ...[more]

PMID: 34522308

Similar Datasets

Redox switchable catalysis utilizing a fluorescent dye.

Project description:This report describes the implementation of a 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY) dye into the ligand framework of a Rh-based catalyst. The redox-active nature of the BODIPY dye is utilized to generate a catalyst that is capable of exhibiting redox-switchable catalytic behavior for the hydroboration of alkenes through a BODIPY-based reduction.

| S-EPMC6953248 | biostudies-literature

Redox-Switchable Complexes Based on Nanographene-NHCs.

Project description:A series of rhodium and iridium complexes with a N-heterocyclic carbene (NHC) ligand decorated with a perylene-diimide-pyrene moiety are described. Electrochemical studies reveal that the complexes can undergo two successive one-electron reduction events, associated to the reduction of the PDI moiety attached to the NHC ligand. The reduction of the ligand produces a significant increase on its electron-donating character, as observed from the infrared spectroelectrochemical studies. The rhodium complex was tested in the [3+2] cycloaddition of diphenylcyclopropenone and methylphenylacetylene, where it displayed a redox-switchable behavior. The neutral complex showed moderate activity, which was suppressed when the catalyst was reduced.

| S-EPMC9400984 | biostudies-literature

Redox-Switchable Allosteric Effects in Molecular Clusters.

Project description:We demonstrate that allosteric effects and redox state changes can be harnessed to create a switch that selectively and reversibly regulates the coordination chemistry of a single site on the surface of a molecular cluster. This redox-switchable allostery is employed as a guiding force to assemble the molecular clusters Zn3Co6Se8L'6 (L' = Ph2PN(H)Tol, Ph = phenyl, Tol = 4-tolyl) into materials of predetermined dimensionality (1- or 2-D) and to encode them with emissive properties. This work paves the path to program the assembly and function of inorganic clusters into stimuli-responsive, atomically precise materials.

| S-EPMC8790731 | biostudies-literature

Comparative sequence, structure and redox analyses of Klebsiella pneumoniae DsbA show that anti-virulence target DsbA enzymes fall into distinct classes.

Project description:Bacterial DsbA enzymes catalyze oxidative folding of virulence factors, and have been identified as targets for antivirulence drugs. However, DsbA enzymes characterized to date exhibit a wide spectrum of redox properties and divergent structural features compared to the prototypical DsbA enzyme of Escherichia coli DsbA (EcDsbA). Nonetheless, sequence analysis shows that DsbAs are more highly conserved than their known substrate virulence factors, highlighting the potential to inhibit virulence across a range of organisms by targeting DsbA. For example, Salmonella enterica typhimurium (SeDsbA, 86 % sequence identity to EcDsbA) shares almost identical structural, surface and redox properties. Using comparative sequence and structure analysis we predicted that five other bacterial DsbAs would share these properties. To confirm this, we characterized Klebsiella pneumoniae DsbA (KpDsbA, 81 % identity to EcDsbA). As expected, the redox properties, structure and surface features (from crystal and NMR data) of KpDsbA were almost identical to those of EcDsbA and SeDsbA. Moreover, KpDsbA and EcDsbA bind peptides derived from their respective DsbBs with almost equal affinity, supporting the notion that compounds designed to inhibit EcDsbA will also inhibit KpDsbA. Taken together, our data show that DsbAs fall into different classes; that DsbAs within a class may be predicted by sequence analysis of binding loops; that DsbAs within a class are able to complement one another in vivo and that compounds designed to inhibit EcDsbA are likely to inhibit DsbAs within the same class.

| S-EPMC3828196 | biostudies-literature

Redox-switchable multicolor luminescent polymers for theragnosis of osteoarthritis.

Project description:Nonaromatic and nonconjugated fluorescent materials have garnered increasing attention in recent years. However, most non-classical chromophores are derived from electro-rich nitrogen and oxygen atoms, which suffer from short emission wavelengths, low efficiency, limited responsiveness, and obscure luminescence mechanisms. Here we present an emission mechanism in bioactive polycysteine, an aliphatic polymer that displays polymerization- and aggregation-induced emission, high quantum yield, and multicolor emission properties. We show that the hydrogen atoms bonded to the sulfur atoms play a crucial role in luminescence. This enables reversible modulation of polymer fluorescence under reducing and oxidizing conditions, facilitating specific imaging and quantitative detection of redox species in cells and in vivo. Furthermore, the polymer exhibits better anti-inflammatory and antioxidative activities compared to first-line clinical antioxidants, offering a promising platform for in vivo theragnosis of diseases such as osteoarthritis.

| S-EPMC11582703 | biostudies-literature

Multistate Redox-Switchable Ion Transport Using Chalcogen-Bonding Anionophores.

Project description:Synthetic supramolecular transmembrane anionophores have emerged as promising anticancer chemotherapeutics. However, key to their targeted application is achieving spatiotemporally controlled activity. Herein, we report a series of chalcogen-bonding diaryl tellurium-based transporters in which their anion binding potency and anionophoric activity are controlled through reversible redox cycling between Te oxidation states. This unprecedented in situ reversible multistate switching allows for switching between ON and OFF anion transport and is crucially achieved with biomimetic chemical redox couples.

| S-EPMC9896566 | biostudies-literature

Redox-Switchable Chalcogen Bonding for Anion Recognition and Sensing.

Project description:Inspired by the success of its related sigma-hole congener halogen bonding (XB), chalcogen bonding (ChB) is emerging as a powerful noncovalent interaction with a plethora of applications in supramolecular chemistry and beyond. Despite its increasing importance, the judicious modulation of ChB donor strength remains a formidable challenge. Herein, we present, for the first time, the reversible and large-scale modulation of ChB potency by electrochemical redox control. This is exemplified by both the switching-ON of anion recognition via ChB oxidative activation of a novel bis(ferrocenyltellurotriazole) anion host and switching-OFF reductive ChB deactivation of anion binding potency with a telluroviologen receptor. The direct linking of the redox-active center and ChB receptor donor sites enables strong coupling, which is reflected by up to a remarkable 3 orders of magnitude modulation of anion binding strength. This is demonstrated through large voltammetric perturbations of the respective receptor ferrocene and viologen redox couples, enabling, for the first time, ChB-mediated electrochemical anion sensing. The sensors not only display significant anion-binding-induced electrochemical responses in competitive aqueous-organic solvent systems but can compete with, or even outperform similar, highly potent XB and HB sensors. These observations serve to highlight a unique (redox) tunability of ChB and pave the way for further exploration of the reversible (redox) modulation of ChB in a wide range of applications, including anion sensors as well as molecular switches and machines.

| S-EPMC9121379 | biostudies-literature

Chiroptical inversion of a planar chiral redox-switchable rotaxane.

Project description:A tetrathiafulvalene (TTF)-containing crown ether macrocycle with C s symmetry was designed to implement planar chirality into a redox-active [2]rotaxane. The directionality of the macrocycle atom sequence together with the non-symmetric axle renders the corresponding [2]rotaxane mechanically planar chiral. Enantiomeric separation of the [2]rotaxane was achieved by chiral HPLC. The electrochemical properties - caused by the reversible oxidation of the TTF - are similar to a non-chiral control. Reversible inversion of the main band in the ECD spectra for the individual enantiomers was observed after oxidation. Experimental evidence, conformational analysis and DFT calculations of the neutral and doubly oxidised species indicate that mainly electronic effects of the oxidation are responsible for the chiroptical switching. This is the first electrochemically switchable rotaxane with a reversible inversion of the main ECD band.

| S-EPMC7003955 | biostudies-literature

Redox-switchable breathing behavior in tetrathiafulvalene-based metal-organic frameworks.

Project description:Metal-organic frameworks (MOFs) that respond to external stimuli such as guest molecules, temperature, or redox conditions are highly desirable. Herein, we coupled redox-switchable properties with breathing behavior induced by guest molecules in a single framework. Guided by topology, two flexible isomeric MOFs, compounds 1 and 2, with a formula of In(Me2NH2)(TTFTB), were constructed via a combination of [In(COO)4]- metal nodes and tetratopic tetrathiafulvalene-based linkers (TTFTB). The two compounds show different breathing behaviors upon the introduction of N2. Single-crystal X-ray diffraction, accompanied by molecular simulations, reveals that the breathing mechanism of 1 involves the bending of metal-ligand bonds and the sliding of interpenetrated frameworks, while 2 undergoes simple distortion of linkers. Reversible oxidation and reduction of TTF moieties changes the linker flexibility, which in turn switches the breathing behavior of 2. The redox-switchable breathing behavior can potentially be applied to the design of stimuli-responsive MOFs.

| S-EPMC5722820 | biostudies-literature

Identification of a redox-regulated chaperone network.

Project description:We have identified and reconstituted a multicomponent redox-chaperone network that appears to be designed to protect proteins against stress-induced unfolding and to refold proteins when conditions return to normal. The central player is Hsp33, a redox-regulated molecular chaperone. Hsp33, which is activated by disulfide bond formation and subsequent dimerization, works as an efficient chaperone holdase that binds to unfolding protein intermediates and maintains them in a folding competent conformation. Reduction of Hsp33 is catalyzed by the glutaredoxin and thioredoxin systems in vivo, and leads to the formation of highly active, reduced Hsp33 dimers. Reduction of Hsp33 is necessary but not sufficient for substrate protein release. Substrate dissociation from Hsp33 is linked to the presence of the DnaK/DnaJ/GrpE foldase system, which alone, or in concert with the GroEL/GroES system, then supports the refolding of the substrate proteins. Upon substrate release, reduced Hsp33 dimers dissociate into inactive monomers. This regulated substrate transfer ultimately links substrate release and Hsp33 inactivation to the presence of available DnaK/DnaJ/GrpE, and, therefore, to the return of cells to non-stress conditions.

| S-EPMC1271656 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data