Bleach Activates a Redox-Regulated Chaperone by Oxidative Protein Unfolding
Hypochlorous acid (HOCl), the active ingredient in household bleach, is an effective antimicrobial produced by the mammalian host defense to kill invading microorganisms. Despite the widespread use of HOCl, surprisingly little is known about its mode of action. In this study, we demonstrate that low...
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| Veröffentlicht in: | Cell 2008-11, Vol.135 (4), p.691-701 |
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| creator | Winter, J. Ilbert, M. Graf, P.C.F. Özcelik, D. Jakob, U. |
| description | Hypochlorous acid (HOCl), the active ingredient in household bleach, is an effective antimicrobial produced by the mammalian host defense to kill invading microorganisms. Despite the widespread use of HOCl, surprisingly little is known about its mode of action. In this study, we demonstrate that low molar ratios of HOCl to protein cause oxidative protein unfolding in vitro and target thermolabile proteins for irreversible aggregation in vivo. As a defense mechanism, bacteria use the redox-regulated chaperone Hsp33, which responds to bleach treatment with the reversible oxidative unfolding of its C-terminal redox switch domain. HOCl-mediated unfolding turns inactive Hsp33 into a highly active chaperone holdase, which protects essential
Escherichia coli proteins against HOCl-induced aggregation and increases bacterial HOCl resistance. Our results substantially improve our molecular understanding about HOCl's functional mechanism. They suggest that the antimicrobial effects of bleach are largely based on HOCl's ability to cause aggregation of essential bacterial proteins. |
| doi_str_mv | 10.1016/j.cell.2008.09.024 |
| format | Article |
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Escherichia coli proteins against HOCl-induced aggregation and increases bacterial HOCl resistance. Our results substantially improve our molecular understanding about HOCl's functional mechanism. They suggest that the antimicrobial effects of bleach are largely based on HOCl's ability to cause aggregation of essential bacterial proteins.</description><subject>CELLBIO</subject><subject>Disulfides</subject><subject>Escherichia coli</subject><subject>Escherichia coli - metabolism</subject><subject>Escherichia coli Proteins - metabolism</subject><subject>Heat-Shock Proteins - metabolism</subject><subject>HUMDISEASE</subject><subject>Hypochlorous Acid - pharmacology</subject><subject>Models, Biological</subject><subject>Molecular Chaperones - metabolism</subject><subject>Molecular Conformation</subject><subject>Oxidation-Reduction</subject><subject>Oxygen - metabolism</subject><subject>Protein Denaturation</subject><subject>Protein Structure, Tertiary</subject><subject>Reactive Oxygen Species</subject><subject>Substrate Specificity</subject><subject>Sulfhydryl Compounds - chemistry</subject><subject>Temperature</subject><issn>0092-8674</issn><issn>1097-4172</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kUtrGzEUhUVpady0f6CLMqvuZnqlkUYjKIXE9EUDKaFZC410ZcuMR640Nsm_r4xNH5uuBFffOfdyDiGvKTQUaPdu01gcx4YB9A2oBhh_QhYUlKw5lewpWQAoVved5BfkRc4bKKAQ4jm5oApoy2S_IN-uRzR2XV3ZORzMjLky1R26-FDf4Wo_lomrlmuzwxQnrIbH6vYhOFNYrL6nOGOYqvvJx9GFafWSPPNmzPjq_F6S-08ffyy_1De3n78ur25qy3s-11wOSnovsfPD4LnjjllumGuHQRgnjJct5y1IOXSyFdB70doeOfVF04Lo20vy4eS72w9bdBanOZlR71LYmvSoown6358prPUqHjTroANFi8Hbs0GKP_eYZ70N-ZilmTDus6ZKdEKJtoDsBNoUc07ofy-hoI8d6I0-6vSxAw1Klw6K6M3f5_2RnEMvwPsTgCWkQ8Cksw04WXQhoZ21i-F__r8ArH6ZtA</recordid><startdate>20081114</startdate><enddate>20081114</enddate><creator>Winter, J.</creator><creator>Ilbert, M.</creator><creator>Graf, P.C.F.</creator><creator>Özcelik, D.</creator><creator>Jakob, U.</creator><general>Elsevier Inc</general><scope>6I.</scope><scope>AAFTH</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QL</scope><scope>7T7</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>P64</scope><scope>5PM</scope></search><sort><creationdate>20081114</creationdate><title>Bleach Activates a Redox-Regulated Chaperone by Oxidative Protein Unfolding</title><author>Winter, J. ; 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| subjects | CELLBIO Disulfides Escherichia coli Escherichia coli - metabolism Escherichia coli Proteins - metabolism Heat-Shock Proteins - metabolism HUMDISEASE Hypochlorous Acid - pharmacology Models, Biological Molecular Chaperones - metabolism Molecular Conformation Oxidation-Reduction Oxygen - metabolism Protein Denaturation Protein Structure, Tertiary Reactive Oxygen Species Substrate Specificity Sulfhydryl Compounds - chemistry Temperature |
| title | Bleach Activates a Redox-Regulated Chaperone by Oxidative Protein Unfolding |
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