Correction: Effect of Interchain Disulfide Bond on Hapten Binding of Light Chain Dimer Protein 315

1980 ◽  
Vol 77 (2) ◽  
pp. 1229-1229
Keyword(s):  
Disulfide Bond ◽  
Light Chain ◽  
Interchain Disulfide Bond ◽  
Chain Dimer ◽  
Correction Effect

scholarly journals A Heterologous Reporter Defines the Role of the Tetanus Toxin Interchain Disulfide in Light-Chain Translocation

2015 ◽  
Vol 83 (7) ◽  
pp. 2714-2724 ◽  
Author(s):  
Madison Zuverink ◽  
Chen Chen ◽  
Amanda Przedpelski ◽  
Faith C. Blum ◽  
Joseph T. Barbieri
Keyword(s):  
Motor Neurons ◽  
Disulfide Bond ◽  
Light Chain ◽  
Tetanus Toxin ◽  
Thioredoxin Reductase ◽  
Single Chain ◽  
Intact Cells ◽  
Spastic Paralysis ◽  
Interchain Disulfide Bond ◽  
N Terminus

Botulinum neurotoxins (BoNTs) and tetanus toxin (TeNT) are the most potent toxins for humans and elicit unique pathologies due to their ability to traffic within motor neurons. BoNTs act locally within motor neurons to elicit flaccid paralysis, while retrograde TeNT traffics to inhibitory neurons within the central nervous system (CNS) to elicit spastic paralysis. BoNT and TeNT are dichain proteins linked by an interchain disulfide bond comprised of an N-terminal catalytic light chain (LC) and a C-terminal heavy chain (HC) that encodes an LC translocation domain (HCT) and a receptor-binding domain (HCR). LC translocation is the least understood property of toxin action, but it involves low pH, proteolysis, and an intact interchain disulfide bridge. Recently, Pirazzini et al. (FEBS Lett 587:150–155, 2013,http://dx.doi.org/10.1016/j.febslet.2012.11.007) observed that inhibitors of thioredoxin reductase (TrxR) blocked TeNT and BoNT action in cerebellar granular neurons. In the current study, an atoxic TeNT LC translocation reporter was engineered by fusing β-lactamase to the N terminus of TeNT [βlac-TeNT(RY)] to investigate LC translocation in primary cortical neurons and Neuro-2a cells. βlac-TeNT(RY) retained the interchain disulfide bond, showed ganglioside-dependent binding to neurons, required acidification to promote βlac translocation, and was sensitive to auranofin, an inhibitor of thioredoxin reductase. Mutation of βlac-TeNT(RY) at C439S and C467S eliminated the interchain disulfide bond and inhibited βlac translocation. These data support the requirement of an intact interchain disulfide for LC translocation and imply that disulfide reduction is a prerequisite for LC delivery into the host cytosol. The data also support a model that LC translocation proceeds from the C to the N terminus. βlac-TeNT(RY) is the first reporter system to measure translocation by an AB single-chain toxin in intact cells.

scholarly journals Effects of an Interchain Disulfide Bond on Tropomyosin Structure: A Molecular Dynamics Study

2018 ◽  
Vol 19 (11) ◽  
pp. 3376 ◽  
Author(s):  
Natalia A. Koubassova ◽  
Sergey Y. Bershitsky ◽  
Andrey K. Tsaturyan
Keyword(s):  
Heart Failure ◽  
Molecular Dynamics ◽  
Disulfide Bond ◽  
Coiled Coil ◽  
Middle Part ◽  
Actin Binding ◽  
Cross Linking ◽  
Interchain Disulfide Bond ◽  
Structural And Functional Properties ◽  
The Cross

Tropomyosin (Tpm) is a coiled-coil actin-binding dimer protein that participates in the regulation of muscle contraction. Both Tpm chains contain Cys190 residues which are normally in the reduced state, but form an interchain disulfide bond in failing heart. Changes in structural and functional properties of Tpm and its complexes with actin upon disulfide cross-linking were studied using various experimental methods. To understand the molecular mechanism underlying these changes and to reveal the possible mechanism of the involvement of the cross-linking in heart failure, molecular dynamics (MD) simulations of the middle part of Tpm were performed in cross-linked and reduced states. The cross-linking increased bending stiffness of Tpm assessed from MD trajectories at 27 °C in agreement with previous experimental observations. However, at 40 °C, the cross-linking caused a decrease in Tpm stiffness and a significant reduction in the number of main chain hydrogen bonds in the vicinity of residues 133 and 134. These data are in line with observations showing enhanced thermal unfolding of the least stable part of Tpm at 30–40 °C and accelerated trypsin cleavage at residue 133 at 40 °C (but not at 27 °C) upon cross-linking. These results allow us to speculate about the possible mechanism of involvement of Tpm cross-linking to heart failure pathogenesis.

scholarly journals A Relaxed Specificity in Interchain Disulfide Bond Formation Characterizes the Assembly of a Low-Molecular-Weight Glutenin Subunit in the Endoplasmic Reticulum

2008 ◽  
Vol 149 (1) ◽  
pp. 412-423 ◽  
Author(s):  
Alessio Lombardi ◽  
Alessandra Barbante ◽  
Pietro Della Cristina ◽  
Daniele Rosiello ◽  
Chiara Lara Castellazzi ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Endoplasmic Reticulum ◽  
Disulfide Bond ◽  
Bond Formation ◽  
Glutenin Subunit ◽  
Low Molecular Weight ◽  
Disulfide Bond Formation ◽  
Interchain Disulfide Bond

Relative Affinity of Plasmin for the α1-Macroglobulin, Cl Inactivator and α1-Antitrypsin Inhibitors

1975 ◽  
Author(s):  
Peter C. Harpel
Keyword(s):  
Complex Formation ◽  
Protease Inhibitors ◽  
Disulfide Bond ◽  
Light Chain ◽  
Binding Sites ◽  
Gel Electrophoresis ◽  
Molar Ratio ◽  
Molar Ratios ◽  
Relative Affinity ◽  
Quantitative Contribution

The quantitative contribution of three major plasma protease inhibitors in binding plasmin has been studied. Mixtures of plasmin and each of the purified inhibitors were analyzed by SDS-acrylamide gel electrophoresis. Plasmin remained bound to its inhibitors in the presence of SDS and urea. A 1 : 1 molar ratio for complex formation was established, and treatment of the complexes with a disulfide bond reducing agent showed that the light chain of plasmin contained the binding sites for both CĪ inactivator and α-antitrysin. Limited degradation of all three inhibitors by plasmin was observed, and the altered inhibitor remained complexed to the enzyme. The competitive binding of 125I plasmin to mixtures of these inhibitors was followed by sucrose density ultracentrifugation and by SDS-gel electrophoresis. In mixtures containing physiologic molar ratios of enzyme and inhibitors, over 80% of the bound plasmin was complexed to the α2-macroglobufui (α2M). No evidence for an exchange of plasmin between the inhibitors was obtained.

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