Control of the toxic conformation of amyloid β42 by intramolecular disulfide bond formation

2020 ◽  
Vol 56 (29) ◽  
pp. 4118-4121 ◽  
Author(s):  
Yuka Matsushima ◽  
Ryo C. Yanagita ◽  
Kazuhiro Irie
Keyword(s):  
Amino Acid ◽  
Disulfide Bond ◽  
Bond Formation ◽  
Disulfide Bond Formation ◽  
Amino Acid Residues ◽  
Intramolecular Disulfide Bond

An Aβ42 analog crosslinked within the molecule at the 17th and 28th amino acid residues exhibited high aggregative ability and potent neurotoxicity comparable to those of E22P-Aβ42.

scholarly journals Disulfide Bond Formation in Secreton Component PulK Provides a Possible Explanation for the Role of DsbA in Pullulanase Secretion

2001 ◽  
Vol 183 (4) ◽  
pp. 1312-1319 ◽  
Author(s):  
Anthony P. Pugsley ◽  
Nicolas Bayan ◽  
Nathalie Sauvonnet
Keyword(s):  
Disulfide Bond ◽  
Klebsiella Oxytoca ◽  
Bond Formation ◽  
Type Ii Secretion ◽  
Disulfide Bond Formation ◽  
Gene Encoding ◽  
Intramolecular Disulfide Bond ◽  
Disulfide Oxidoreductase ◽  
Considerable Excess

ABSTRACT When expressed in Escherichia coli, the 15Klebsiella oxytoca pul genes that encode the so-called Pul secreton or type II secretion machinery promote pullulanase secretion and the assembly of one of the secreton components, PulG, into pili. Besides these pul genes, efficient pullulanase secretion also requires the host dsbA gene, encoding a periplasmic disulfide oxidoreductase, independently of disulfide bond formation in pullulanase itself. Two secreton components, the secretin pilot protein PulS and the minor pseudopilin PulK, were each shown to posses an intramolecular disulfide bond whose formation was catalyzed by DsbA. PulS was apparently destabilized by the absence of its disulfide bond, whereas PulK stability was not dramatically affected either by adsbA mutation or by the removal of one of its cysteines. The pullulanase secretion defect in a dsbA mutant was rectified by overproduction of PulK, indicating reduced disulfide bond formation in PulK as the major cause of the secretion defect under the conditions tested (in which PulS is probably present in considerable excess of requirements). PulG pilus formation was independent of DsbA, probably because PulK is not needed for piliation.

Inhibition of Human Cytomegalovirus UL80 Protease by Specific Intramolecular Disulfide Bond Formation†

Biochemistry ◽  
1996 ◽  
Vol 35 (18) ◽  
pp. 5838-5846 ◽  
Author(s):  
Ellen Z. Baum ◽  
Marshall M. Siegel ◽  
Geraldine A. Bebernitz ◽  
Jeffrey D. Hulmes ◽  
Latha Sridharan ◽  
...  
Keyword(s):  
Human Cytomegalovirus ◽  
Disulfide Bond ◽  
Bond Formation ◽  
Disulfide Bond Formation ◽  
Intramolecular Disulfide Bond

Charcoal surface-assisted catalysis of intramolecular disulfide bond formation in peptides

2009 ◽  
Vol 51 (5) ◽  
pp. 365-369 ◽  
Author(s):  
RUDOLF VOLKMER-ENGERT ◽  
CHRISTIANE LANDGRAF ◽  
JENS SCHNEIDER-MERGENER
Keyword(s):  
Disulfide Bond ◽  
Bond Formation ◽  
Disulfide Bond Formation ◽  
Intramolecular Disulfide Bond

scholarly journals Role of the Intramolecular Disulfide Bond in FlgI, the Flagellar P-Ring Component of Escherichia coli

2006 ◽  
Vol 188 (12) ◽  
pp. 4190-4197 ◽  
Author(s):  
Yohei Hizukuri ◽  
Toshiharu Yakushi ◽  
Ikuro Kawagishi ◽  
Michio Homma
Keyword(s):  
Escherichia Coli ◽  
Disulfide Bond ◽  
Self Assembly ◽  
Bacterial Species ◽  
Bond Formation ◽  
Disulfide Bond Formation ◽  
Wild Type ◽  
Ring Assembly ◽  
Intramolecular Disulfide Bond

ABSTRACT The P ring of the bacterial flagellar motor consists of multiple copies of FlgI, a periplasmic protein. The intramolecular disulfide bond in FlgI has previously been reported to be essential for P-ring assembly in Escherichia coli, because the P ring was not assembled in a dsbB strain that was defective for disulfide bond formation in periplasmic proteins. We, however, found that the two Cys residues of FlgI are not conserved in other bacterial species. We then assessed the role of this intramolecular disulfide bond in FlgI. A Cys-eliminated FlgI derivative formed a P ring that complemented the flagellation defect of our ΔflgI strain when it was overproduced, suggesting that disulfide bond formation in FlgI is not absolutely required for P-ring assembly. The levels of the mature forms of the FlgI derivatives were significantly lower than that of wild-type FlgI, although the precursor protein levels were unchanged. Moreover, the FlgI derivatives were more susceptible to degradation than wild-type FlgI. Overproduction of FlgI suppressed the motility defect of ΔdsbB cells. Additionally, the low level of FlgI observed in the ΔdsbB strain increased in the presence of l-cystine, an oxidative agent. We propose that intramolecular disulfide bond formation facilitates the rapid folding of the FlgI monomer to protect against degradation in the periplasmic space, thereby allowing its efficient self-assembly into the P ring.

scholarly journals H2O2-Mediated Oxidative Stress Enhances Cystathionine γ-Lyase-Derived H2S Synthesis via a Sulfenic Acid Intermediate

Antioxidants ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 1488
Author(s):  
Jun Wang ◽  
Guanya Jia ◽  
Heng Li ◽  
Shasha Yan ◽  
Jing Qian ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Disulfide Bond ◽  
Bond Formation ◽  
Thiol Group ◽  
Disulfide Bond Formation ◽  
Sulfenic Acid ◽  
Intramolecular Disulfide Bond ◽  
Wide Range ◽  
Endothelial Growth Factor ◽  
H2s Production

Hydrogen sulfide (H2S), which is generated mainly by cystathionine γ-lyase (CSE) in the cardiovascular system, plays a pivotal role in a wide range of physiological and pathological processes. However, the regulatory mechanism of the CSE/H2S system is poorly understood. Herein, we show that oxidation induces the disulfide bond formation between Cys252 and Cys255 in the CXXC motif, thus stimulating the H2S-producing activity of CSE. The activity of oxidized CSE is approximately 2.5 fold greater than that of the reduced enzyme. Molecular dynamics and molecular docking suggest that the disulfide bond formation induces the conformational change in the active site of CSE and consequently increases the affinity of the enzyme for the substrate L-cysteine. Mass spectrometry and mutagenesis studies further established that the residue Cys255 is crucial for oxidation sensing. Oxidative stress-mediated sulfenylation of Cys255 leads to a sulfenic acid intermediate that spontaneously forms an intramolecular disulfide bond with the vicinal thiol group of Cys252. Moreover, we demonstrate that exogenous hydrogen peroxide (H2O2) and endogenous H2O2 triggered by vascular endothelial growth factor (VEGF) promote cellular H2S production through the enhancement of CSE activity under oxidative stress conditions. By contrast, incubation with H2O2 or VEGF did not significantly enhance cellular H2S production in the presence of PEG-catalase, an enzymatic cell-permeable H2O2 scavenger with high H2O2 specificity. Taken together, we report a new posttranslational modification of CSE that provides a molecular mechanism for H2O2/H2S crosstalk in cells under oxidative stress.

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