The Hsp90 machinery facilitates the transport of diphtheria toxin into human cells
Abstract Diphtheria toxin kills human cells because it delivers its enzyme domain DTA into their cytosol where it inhibits protein synthesis. After receptor-mediated uptake of the toxin, DTA translocates from acidic endosomes into the cytosol, which might be assisted by host cell factors. Here we in...
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2017
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oai:doaj.org-article:ae633d2015bd44bcb353d2cd6cd6a6082021-12-02T11:52:59ZThe Hsp90 machinery facilitates the transport of diphtheria toxin into human cells10.1038/s41598-017-00780-x2045-2322https://doaj.org/article/ae633d2015bd44bcb353d2cd6cd6a6082017-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-00780-xhttps://doaj.org/toc/2045-2322Abstract Diphtheria toxin kills human cells because it delivers its enzyme domain DTA into their cytosol where it inhibits protein synthesis. After receptor-mediated uptake of the toxin, DTA translocates from acidic endosomes into the cytosol, which might be assisted by host cell factors. Here we investigated the role of Hsp90 and its co-chaperones during the uptake of native diphtheria toxin into human cells and identified the components of the Hsp90 machinery including Hsp90, Hsp70, Cyp40 and the FK506 binding proteins FKBP51 and FKBP52 as DTA binding partners. Moreover, pharmacological inhibition of the chaperone activity of Hsp90 and Hsp70 and of the peptidyl-prolyl cis/trans isomerase (PPIase) activity of Cyps and FKBPs protected cells from intoxication with diphtheria toxin and inhibited the pH-dependent trans-membrane transport of DTA into the cytosol. In conclusion, these host cell factors facilitate toxin uptake into human cells, which might lead to development of novel therapeutic strategies against diphtheria.Manuel SchusterLeonie SchnellPeter FeiglCarina BirkhoferKatharina MohrMaurice RoederStefan CarleSimon LangerFranziska TippelJohannes BuchnerGunter FischerFelix HauschManfred FrickCarsten SchwanKlaus AktoriesCordelia Schiene-FischerHolger BarthNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-14 (2017) |
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DOAJ |
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Medicine R Science Q |
| spellingShingle |
Medicine R Science Q Manuel Schuster Leonie Schnell Peter Feigl Carina Birkhofer Katharina Mohr Maurice Roeder Stefan Carle Simon Langer Franziska Tippel Johannes Buchner Gunter Fischer Felix Hausch Manfred Frick Carsten Schwan Klaus Aktories Cordelia Schiene-Fischer Holger Barth The Hsp90 machinery facilitates the transport of diphtheria toxin into human cells |
| description |
Abstract Diphtheria toxin kills human cells because it delivers its enzyme domain DTA into their cytosol where it inhibits protein synthesis. After receptor-mediated uptake of the toxin, DTA translocates from acidic endosomes into the cytosol, which might be assisted by host cell factors. Here we investigated the role of Hsp90 and its co-chaperones during the uptake of native diphtheria toxin into human cells and identified the components of the Hsp90 machinery including Hsp90, Hsp70, Cyp40 and the FK506 binding proteins FKBP51 and FKBP52 as DTA binding partners. Moreover, pharmacological inhibition of the chaperone activity of Hsp90 and Hsp70 and of the peptidyl-prolyl cis/trans isomerase (PPIase) activity of Cyps and FKBPs protected cells from intoxication with diphtheria toxin and inhibited the pH-dependent trans-membrane transport of DTA into the cytosol. In conclusion, these host cell factors facilitate toxin uptake into human cells, which might lead to development of novel therapeutic strategies against diphtheria. |
| format |
article |
| author |
Manuel Schuster Leonie Schnell Peter Feigl Carina Birkhofer Katharina Mohr Maurice Roeder Stefan Carle Simon Langer Franziska Tippel Johannes Buchner Gunter Fischer Felix Hausch Manfred Frick Carsten Schwan Klaus Aktories Cordelia Schiene-Fischer Holger Barth |
| author_facet |
Manuel Schuster Leonie Schnell Peter Feigl Carina Birkhofer Katharina Mohr Maurice Roeder Stefan Carle Simon Langer Franziska Tippel Johannes Buchner Gunter Fischer Felix Hausch Manfred Frick Carsten Schwan Klaus Aktories Cordelia Schiene-Fischer Holger Barth |
| author_sort |
Manuel Schuster |
| title |
The Hsp90 machinery facilitates the transport of diphtheria toxin into human cells |
| title_short |
The Hsp90 machinery facilitates the transport of diphtheria toxin into human cells |
| title_full |
The Hsp90 machinery facilitates the transport of diphtheria toxin into human cells |
| title_fullStr |
The Hsp90 machinery facilitates the transport of diphtheria toxin into human cells |
| title_full_unstemmed |
The Hsp90 machinery facilitates the transport of diphtheria toxin into human cells |
| title_sort |
hsp90 machinery facilitates the transport of diphtheria toxin into human cells |
| publisher |
Nature Portfolio |
| publishDate |
2017 |
| url |
https://doaj.org/article/ae633d2015bd44bcb353d2cd6cd6a608 |
| work_keys_str_mv |
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