Structure and Mechanism of Action of Sda, an Inhibitor of the Histidine Kinases that Regulate Initiation of Sporulation in Bacillus subtilis
Histidine kinases are used extensively in prokaryotes to monitor and respond to changes in cellular and environmental conditions. In Bacillus subtilis, sporulation-specific gene expression is controlled by a histidine kinase phosphorelay that culminates in phosphorylation of the Spo0A transcription...
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| Format: | Article |
| Language: | en_US |
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Elsevier
2014
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| Online Access: | http://hdl.handle.net/1721.1/83848 https://orcid.org/0000-0002-8235-7227 |
| _version_ | 1811079343772794880 |
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| author | Rowland, Susan L. Burkholder, William F. Cunningham, Katherine A. Maciejewski, Mark W. King, Glenn F. Grossman, Alan Davis |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Rowland, Susan L. Burkholder, William F. Cunningham, Katherine A. Maciejewski, Mark W. King, Glenn F. Grossman, Alan Davis |
| author_sort | Rowland, Susan L. |
| collection | MIT |
| description | Histidine kinases are used extensively in prokaryotes to monitor and respond to changes in cellular and environmental conditions. In Bacillus subtilis, sporulation-specific gene expression is controlled by a histidine kinase phosphorelay that culminates in phosphorylation of the Spo0A transcription factor. Sda provides a developmental checkpoint by inhibiting this phosphorelay in response to DNA damage and replication defects. We show that Sda acts at the first step in the relay by inhibiting autophosphorylation of the histidine kinase KinA. The structure of Sda, which we determined using NMR, comprises a helical hairpin. A cluster of conserved residues on one face of the hairpin mediates an interaction between Sda and the KinA dimerization/phosphotransfer domain. This interaction stabilizes the KinA dimer, and the two proteins form a stable heterotetramer. The data indicate that Sda forms a molecular barricade that inhibits productive interaction between the catalytic and phosphotransfer domains of KinA. |
| first_indexed | 2024-09-23T11:13:42Z |
| format | Article |
| id | mit-1721.1/83848 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T11:13:42Z |
| publishDate | 2014 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | mit-1721.1/838482022-10-01T02:10:54Z Structure and Mechanism of Action of Sda, an Inhibitor of the Histidine Kinases that Regulate Initiation of Sporulation in Bacillus subtilis Rowland, Susan L. Burkholder, William F. Cunningham, Katherine A. Maciejewski, Mark W. King, Glenn F. Grossman, Alan Davis Massachusetts Institute of Technology. Department of Biology Burkholder, William F. Grossman, Alan D. Histidine kinases are used extensively in prokaryotes to monitor and respond to changes in cellular and environmental conditions. In Bacillus subtilis, sporulation-specific gene expression is controlled by a histidine kinase phosphorelay that culminates in phosphorylation of the Spo0A transcription factor. Sda provides a developmental checkpoint by inhibiting this phosphorelay in response to DNA damage and replication defects. We show that Sda acts at the first step in the relay by inhibiting autophosphorylation of the histidine kinase KinA. The structure of Sda, which we determined using NMR, comprises a helical hairpin. A cluster of conserved residues on one face of the hairpin mediates an interaction between Sda and the KinA dimerization/phosphotransfer domain. This interaction stabilizes the KinA dimer, and the two proteins form a stable heterotetramer. The data indicate that Sda forms a molecular barricade that inhibits productive interaction between the catalytic and phosphotransfer domains of KinA. National Institutes of Health (U.S.) (GM41934) American Cancer Society (Postdoctoral Fellowship) Merck/MIT Collaborative Program 2014-01-10T14:37:37Z 2014-01-10T14:37:37Z 2004-03 2004-01 Article http://purl.org/eprint/type/JournalArticle 10972765 1097-4164 http://hdl.handle.net/1721.1/83848 Rowland, Susan L. et al. “Structure and Mechanism of Action of Sda, an Inhibitor of the Histidine Kinases That Regulate Initiation of Sporulation in Bacillus Subtilis.” Molecular Cell 13.5 (2004): 689–701. Copyright © 2004 Cell Press https://orcid.org/0000-0002-8235-7227 en_US http://dx.doi.org/10.1016/S1097-2765(04)00084-X Molecular Cell Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf Elsevier Elsevier Open Archive |
| spellingShingle | Rowland, Susan L. Burkholder, William F. Cunningham, Katherine A. Maciejewski, Mark W. King, Glenn F. Grossman, Alan Davis Structure and Mechanism of Action of Sda, an Inhibitor of the Histidine Kinases that Regulate Initiation of Sporulation in Bacillus subtilis |
| title | Structure and Mechanism of Action of Sda, an Inhibitor of the Histidine Kinases that Regulate Initiation of Sporulation in Bacillus subtilis |
| title_full | Structure and Mechanism of Action of Sda, an Inhibitor of the Histidine Kinases that Regulate Initiation of Sporulation in Bacillus subtilis |
| title_fullStr | Structure and Mechanism of Action of Sda, an Inhibitor of the Histidine Kinases that Regulate Initiation of Sporulation in Bacillus subtilis |
| title_full_unstemmed | Structure and Mechanism of Action of Sda, an Inhibitor of the Histidine Kinases that Regulate Initiation of Sporulation in Bacillus subtilis |
| title_short | Structure and Mechanism of Action of Sda, an Inhibitor of the Histidine Kinases that Regulate Initiation of Sporulation in Bacillus subtilis |
| title_sort | structure and mechanism of action of sda an inhibitor of the histidine kinases that regulate initiation of sporulation in bacillus subtilis |
| url | http://hdl.handle.net/1721.1/83848 https://orcid.org/0000-0002-8235-7227 |
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