ToxR activates the Vibrio cholerae virulence genes by tethering DNA to the membrane through versatile binding to multiple sites
ToxR, a transmembrane one-component signal transduction factor, lies within a regulatory cascade that results in the expression of ToxT, toxin coregulated pilus, and cholera toxin. While ToxR has been extensively studied for its ability to activate or repress various genes in , here we present the c...
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| Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 2023-07, Vol.120 (29), p.e2304378120-e2304378120 |
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| container_title | Proceedings of the National Academy of Sciences - PNAS |
| container_volume | 120 |
| creator | Canals, Albert Pieretti, Simone Muriel-Masanes, Mireia El Yaman, Nour Plecha, Sarah C Thomson, Joshua J Fàbrega-Ferrer, Montserrat Pérez-Luque, Rosa Krukonis, Eric S Coll, Miquel |
| description | ToxR, a
transmembrane one-component signal transduction factor, lies within a regulatory cascade that results in the expression of ToxT, toxin coregulated pilus, and cholera toxin. While ToxR has been extensively studied for its ability to activate or repress various genes in
, here we present the crystal structures of the ToxR cytoplasmic domain bound to DNA at the
and
promoters. The structures confirm some predicted interactions, yet reveal other unexpected promoter interactions with implications for other potential regulatory roles for ToxR. We show that ToxR is a versatile virulence regulator that recognizes diverse and extensive, eukaryotic-like regulatory DNA sequences, that relies more on DNA structural elements than specific sequences for binding. Using this topological DNA recognition mechanism, ToxR can bind both in tandem and in a twofold inverted-repeat-driven manner. Its regulatory action is based on coordinated multiple binding to promoter regions near the transcription start site, which can remove the repressing H-NS proteins and prepares the DNA for optimal interaction with the RNA polymerase. |
| doi_str_mv | 10.1073/PNAS.2304378120 |
| format | Article |
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transmembrane one-component signal transduction factor, lies within a regulatory cascade that results in the expression of ToxT, toxin coregulated pilus, and cholera toxin. While ToxR has been extensively studied for its ability to activate or repress various genes in
, here we present the crystal structures of the ToxR cytoplasmic domain bound to DNA at the
and
promoters. The structures confirm some predicted interactions, yet reveal other unexpected promoter interactions with implications for other potential regulatory roles for ToxR. We show that ToxR is a versatile virulence regulator that recognizes diverse and extensive, eukaryotic-like regulatory DNA sequences, that relies more on DNA structural elements than specific sequences for binding. Using this topological DNA recognition mechanism, ToxR can bind both in tandem and in a twofold inverted-repeat-driven manner. Its regulatory action is based on coordinated multiple binding to promoter regions near the transcription start site, which can remove the repressing H-NS proteins and prepares the DNA for optimal interaction with the RNA polymerase.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/PNAS.2304378120</identifier><identifier>PMID: 37428913</identifier><language>eng</language><publisher>United States: National Academy of Sciences</publisher><subject>Bacteria ; Bacterial Proteins - metabolism ; Binding ; Biological Sciences ; Cholera ; Cholera toxin ; Deoxyribonucleic acid ; DNA ; DNA - genetics ; DNA - metabolism ; DNA-Binding Proteins - metabolism ; DNA-directed RNA polymerase ; Gene Expression Regulation, Bacterial ; Gene sequencing ; Genes ; Nucleotide sequence ; Physical Sciences ; RNA polymerase ; Signal transduction ; Structural members ; Tethering ; Toxins ; Transcription Factors - metabolism ; Transcription initiation ; Vibrio cholerae ; Vibrio cholerae - metabolism ; Virulence ; Waterborne diseases</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 2023-07, Vol.120 (29), p.e2304378120-e2304378120</ispartof><rights>Copyright National Academy of Sciences Jul 18, 2023</rights><rights>Copyright © 2023 the Author(s). Published by PNAS. 2023</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c422t-7cc817ab16bea0b451423ca35f25f3114c35f56a8c0ce51395cdba6c305834f23</citedby><cites>FETCH-LOGICAL-c422t-7cc817ab16bea0b451423ca35f25f3114c35f56a8c0ce51395cdba6c305834f23</cites><orcidid>0000-0002-4400-3612 ; 0000-0003-0429-9348 ; 0000-0002-3267-2632</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC10629549/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC10629549/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/37428913$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Canals, Albert</creatorcontrib><creatorcontrib>Pieretti, Simone</creatorcontrib><creatorcontrib>Muriel-Masanes, Mireia</creatorcontrib><creatorcontrib>El Yaman, Nour</creatorcontrib><creatorcontrib>Plecha, Sarah C</creatorcontrib><creatorcontrib>Thomson, Joshua J</creatorcontrib><creatorcontrib>Fàbrega-Ferrer, Montserrat</creatorcontrib><creatorcontrib>Pérez-Luque, Rosa</creatorcontrib><creatorcontrib>Krukonis, Eric S</creatorcontrib><creatorcontrib>Coll, Miquel</creatorcontrib><title>ToxR activates the Vibrio cholerae virulence genes by tethering DNA to the membrane through versatile binding to multiple sites</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>ToxR, a
transmembrane one-component signal transduction factor, lies within a regulatory cascade that results in the expression of ToxT, toxin coregulated pilus, and cholera toxin. While ToxR has been extensively studied for its ability to activate or repress various genes in
, here we present the crystal structures of the ToxR cytoplasmic domain bound to DNA at the
and
promoters. The structures confirm some predicted interactions, yet reveal other unexpected promoter interactions with implications for other potential regulatory roles for ToxR. We show that ToxR is a versatile virulence regulator that recognizes diverse and extensive, eukaryotic-like regulatory DNA sequences, that relies more on DNA structural elements than specific sequences for binding. Using this topological DNA recognition mechanism, ToxR can bind both in tandem and in a twofold inverted-repeat-driven manner. Its regulatory action is based on coordinated multiple binding to promoter regions near the transcription start site, which can remove the repressing H-NS proteins and prepares the DNA for optimal interaction with the RNA polymerase.</description><subject>Bacteria</subject><subject>Bacterial Proteins - metabolism</subject><subject>Binding</subject><subject>Biological Sciences</subject><subject>Cholera</subject><subject>Cholera toxin</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA - genetics</subject><subject>DNA - metabolism</subject><subject>DNA-Binding Proteins - metabolism</subject><subject>DNA-directed RNA polymerase</subject><subject>Gene Expression Regulation, Bacterial</subject><subject>Gene sequencing</subject><subject>Genes</subject><subject>Nucleotide sequence</subject><subject>Physical Sciences</subject><subject>RNA polymerase</subject><subject>Signal transduction</subject><subject>Structural members</subject><subject>Tethering</subject><subject>Toxins</subject><subject>Transcription Factors - metabolism</subject><subject>Transcription initiation</subject><subject>Vibrio cholerae</subject><subject>Vibrio cholerae - metabolism</subject><subject>Virulence</subject><subject>Waterborne diseases</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkUtvEzEUhS0EomlhzQ5ZYsNmWj9nPCsUFQpIVUFQ2Fq2cydxNWOntieiK_46Di0RsPLrO9fn6CD0gpJTSjp-9vlq-fWUcSJ4pygjj9CCkp42rejJY7QghHWNEkwcoeOcbwghvVTkKTrinWCqp3yBfl7HH1-wccXvTIGMywbwd2-Tj9ht4gjJAN75NI8QHOA1hMrYO1yggsmHNX57tcQl_tZNMNlkAtRDivN6g3eQsil-BGx9WO3pSk7zWPy23mVfP3yGngxmzPD8YT1B3y7eXZ9_aC4_vf94vrxsnGCsNJ1zinbG0taCIVZIKhh3hsuByYFTKlzdytYoRxxIynvpVta0jhOpuBgYP0Fv7uduZzvBykEoyYx6m_xk0p2Oxut_X4Lf6HXcaUpa1kvR1wmvHyakeDtDLnry2cE41sRxzpopXsm2V11FX_2H3sQ5hZqvUoK0straWzq7p1yKOScYDm4o0ft29TaYqji0WxUv_w5x4P_UyX8BXGWimQ</recordid><startdate>20230718</startdate><enddate>20230718</enddate><creator>Canals, Albert</creator><creator>Pieretti, Simone</creator><creator>Muriel-Masanes, Mireia</creator><creator>El Yaman, Nour</creator><creator>Plecha, Sarah C</creator><creator>Thomson, Joshua J</creator><creator>Fàbrega-Ferrer, Montserrat</creator><creator>Pérez-Luque, Rosa</creator><creator>Krukonis, Eric S</creator><creator>Coll, Miquel</creator><general>National Academy of Sciences</general><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>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-4400-3612</orcidid><orcidid>https://orcid.org/0000-0003-0429-9348</orcidid><orcidid>https://orcid.org/0000-0002-3267-2632</orcidid></search><sort><creationdate>20230718</creationdate><title>ToxR activates the Vibrio cholerae virulence genes by tethering DNA to the membrane through versatile binding to multiple sites</title><author>Canals, Albert ; Pieretti, Simone ; Muriel-Masanes, Mireia ; El Yaman, Nour ; Plecha, Sarah C ; Thomson, Joshua J ; Fàbrega-Ferrer, Montserrat ; Pérez-Luque, Rosa ; Krukonis, Eric S ; Coll, Miquel</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c422t-7cc817ab16bea0b451423ca35f25f3114c35f56a8c0ce51395cdba6c305834f23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Bacteria</topic><topic>Bacterial Proteins - metabolism</topic><topic>Binding</topic><topic>Biological Sciences</topic><topic>Cholera</topic><topic>Cholera toxin</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>DNA - genetics</topic><topic>DNA - metabolism</topic><topic>DNA-Binding Proteins - metabolism</topic><topic>DNA-directed RNA polymerase</topic><topic>Gene Expression Regulation, Bacterial</topic><topic>Gene sequencing</topic><topic>Genes</topic><topic>Nucleotide sequence</topic><topic>Physical Sciences</topic><topic>RNA polymerase</topic><topic>Signal transduction</topic><topic>Structural members</topic><topic>Tethering</topic><topic>Toxins</topic><topic>Transcription Factors - metabolism</topic><topic>Transcription initiation</topic><topic>Vibrio cholerae</topic><topic>Vibrio cholerae - metabolism</topic><topic>Virulence</topic><topic>Waterborne diseases</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Canals, Albert</creatorcontrib><creatorcontrib>Pieretti, Simone</creatorcontrib><creatorcontrib>Muriel-Masanes, Mireia</creatorcontrib><creatorcontrib>El Yaman, Nour</creatorcontrib><creatorcontrib>Plecha, Sarah C</creatorcontrib><creatorcontrib>Thomson, Joshua J</creatorcontrib><creatorcontrib>Fàbrega-Ferrer, Montserrat</creatorcontrib><creatorcontrib>Pérez-Luque, Rosa</creatorcontrib><creatorcontrib>Krukonis, Eric S</creatorcontrib><creatorcontrib>Coll, Miquel</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Canals, Albert</au><au>Pieretti, Simone</au><au>Muriel-Masanes, Mireia</au><au>El Yaman, Nour</au><au>Plecha, Sarah C</au><au>Thomson, Joshua J</au><au>Fàbrega-Ferrer, Montserrat</au><au>Pérez-Luque, Rosa</au><au>Krukonis, Eric S</au><au>Coll, Miquel</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>ToxR activates the Vibrio cholerae virulence genes by tethering DNA to the membrane through versatile binding to multiple sites</atitle><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle><addtitle>Proc Natl Acad Sci U S A</addtitle><date>2023-07-18</date><risdate>2023</risdate><volume>120</volume><issue>29</issue><spage>e2304378120</spage><epage>e2304378120</epage><pages>e2304378120-e2304378120</pages><issn>0027-8424</issn><eissn>1091-6490</eissn><abstract>ToxR, a
transmembrane one-component signal transduction factor, lies within a regulatory cascade that results in the expression of ToxT, toxin coregulated pilus, and cholera toxin. While ToxR has been extensively studied for its ability to activate or repress various genes in
, here we present the crystal structures of the ToxR cytoplasmic domain bound to DNA at the
and
promoters. The structures confirm some predicted interactions, yet reveal other unexpected promoter interactions with implications for other potential regulatory roles for ToxR. We show that ToxR is a versatile virulence regulator that recognizes diverse and extensive, eukaryotic-like regulatory DNA sequences, that relies more on DNA structural elements than specific sequences for binding. Using this topological DNA recognition mechanism, ToxR can bind both in tandem and in a twofold inverted-repeat-driven manner. Its regulatory action is based on coordinated multiple binding to promoter regions near the transcription start site, which can remove the repressing H-NS proteins and prepares the DNA for optimal interaction with the RNA polymerase.</abstract><cop>United States</cop><pub>National Academy of Sciences</pub><pmid>37428913</pmid><doi>10.1073/PNAS.2304378120</doi><orcidid>https://orcid.org/0000-0002-4400-3612</orcidid><orcidid>https://orcid.org/0000-0003-0429-9348</orcidid><orcidid>https://orcid.org/0000-0002-3267-2632</orcidid><oa>free_for_read</oa></addata></record> |
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| ispartof | Proceedings of the National Academy of Sciences - PNAS, 2023-07, Vol.120 (29), p.e2304378120-e2304378120 |
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| source | MEDLINE; PubMed Central; Alma/SFX Local Collection; Free Full-Text Journals in Chemistry |
| subjects | Bacteria Bacterial Proteins - metabolism Binding Biological Sciences Cholera Cholera toxin Deoxyribonucleic acid DNA DNA - genetics DNA - metabolism DNA-Binding Proteins - metabolism DNA-directed RNA polymerase Gene Expression Regulation, Bacterial Gene sequencing Genes Nucleotide sequence Physical Sciences RNA polymerase Signal transduction Structural members Tethering Toxins Transcription Factors - metabolism Transcription initiation Vibrio cholerae Vibrio cholerae - metabolism Virulence Waterborne diseases |
| title | ToxR activates the Vibrio cholerae virulence genes by tethering DNA to the membrane through versatile binding to multiple sites |
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