ArticleJournal of molecular biology2010
Conformational switching of the diphtheria toxin T domain.
Article in Journal of molecular biology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed.
- Constant-pH MD simulations of the protonation-triggered conformational switching in diphtheria toxin translocation domain.Biophysical journal · 2024Article
- Optimization of a Modular Nanotransporter Design for Targeted Intracellular Delivery of Photosensitizer.Pharmaceutics · 2024Article
- Fluorescent Probes and Quenchers in Studies of Protein Folding and Protein-Lipid Interactions.Chemical record (New York, N.Y.) · 2024Review
- Histidine Protonation and Conformational Switching in Diphtheria Toxin Translocation Domain.Toxins · 2023Article
- Structures of distant diphtheria toxin homologs reveal functional determinants of an evolutionarily conserved toxin scaffold.Communications biology · 2022Article
- Conformational switching, refolding and membrane insertion of the diphtheria toxin translocation domain.Methods in enzymology · 2021Article
- Article
- Review
- Article
- The pH-Dependent Trigger in Diphtheria Toxin T Domain Comes with a Safety Latch.Biophysical journal · 2016Article
- Ionization Properties of Histidine Residues in the Lipid Bilayer Membrane Environment.The Journal of biological chemistry · 2016Article
- DT(270-326) , a Truncated Diphtheria Toxin, Increases Blood-Tumor Barrier Permeability by Upregulating the Expression of Caveolin-1.CNS neuroscience & therapeutics · 2016Article
- Membrane Association of the Diphtheria Toxin Translocation Domain Studied by Coarse-Grained Simulations and Experiment.The Journal of membrane biology · 2015Article
- Calibration of Distribution Analysis of the Depth of Membrane Penetration Using Simulations and Depth-Dependent Fluorescence Quenching.The Journal of membrane biology · 2015Article
- Thermodynamics of Membrane Insertion and Refolding of the Diphtheria Toxin T-Domain.The Journal of membrane biology · 2015Article
- Role of acidic residues in helices TH8-TH9 in membrane interactions of the diphtheria toxin T domain.Toxins · 2015Article
- Membrane translocation assay based on proteolytic cleavage: application to diphtheria toxin T domain.Biochimica et biophysica acta · 2015Article
- Glutamate 85 and glutamate 228 contribute to the pH-response of the soluble form of chloride intracellular channel 1.Molecular and cellular biochemistry · 2015Article
- Hydrogen-deuterium exchange and mass spectrometry reveal the pH-dependent conformational changes of diphtheria toxin T domain.Biochemistry · 2014Article
- Comparison of membrane insertion pathways of the apoptotic regulator Bcl-xL and the diphtheria toxin translocation domain.Biochemistry · 2013Article
Corrections and comments
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Authors and funding
8 authors.
Funding
Abstract
The diphtheria toxin T domain translocates the catalytic C domain across the endosomal membrane in response to acidification. To elucidate the role of histidine protonation in modulating pH-dependent membrane action of the T domain, we have used site-directed mutagenesis coupled with spectroscopic and physiological assays. Replacement of H257 with an arginine (but not with a glutamine) resulted in dramatic unfolding of the protein at neutral pH, accompanied by a substantial loss of helical structure and greatly increased exposure of the buried residues W206 and W281. This unfolding and spectral shift could be reversed by the interaction of the H257R mutant with model lipid membranes. Remarkably, this greatly unfolded mutant exhibited wild-type-like activity in channel formation, N-terminus translocation, and cytotoxicity assays. Moreover, membrane permeabilization caused by the H257R mutant occurs already at pH 6, where wild type protein is inactive. We conclude that protonation of H257 acts as a major component of the pH-dependent conformational switch, resulting in destabilization of the folded structure in solution and thereby promoting the initial membrane interactions necessary for translocation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.