Identification of the SlmA active site responsible for blocking bacterial cytokinetic ring assembly over the chromosome.
Bacterial cells use chromosome-associated division inhibitors to help coordinate the processes of DNA replication and segregation with cytokinesis. SlmA from Escherichia coli, a member of the tetracycline repressor (TetR)-like protein family, is one example of this class of regulator. It blocks the...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS Genetics |
| Online Access: | http://europepmc.org/articles/PMC3573117?pdf=render |
| _version_ | 1819206160152002560 |
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| author | Hongbaek Cho Thomas G Bernhardt |
| author_facet | Hongbaek Cho Thomas G Bernhardt |
| author_sort | Hongbaek Cho |
| collection | DOAJ |
| description | Bacterial cells use chromosome-associated division inhibitors to help coordinate the processes of DNA replication and segregation with cytokinesis. SlmA from Escherichia coli, a member of the tetracycline repressor (TetR)-like protein family, is one example of this class of regulator. It blocks the assembly of the bacterial cytokinetic ring by interfering with the polymerization of the tubulin-like FtsZ protein in a manner that is dramatically stimulated upon specific DNA binding. Here we used a combination of molecular genetics and biochemistry to identify the active site of SlmA responsible for disrupting FtsZ polymerization. Interestingly, this site maps to a region of SlmA that in the published DNA-free structure is partially occluded by the DNA-binding domains. In this conformation, the SlmA structure resembles the drug/inducer-bound conformers of other TetR-like proteins, which in the absence of inducer require an inward rotation of their DNA-binding domains to bind successive major grooves on operator DNA. Our results are therefore consistent with a model in which DNA-binding activates SlmA by promoting a rotational movement of the DNA-binding domains that fully exposes the FtsZ-binding sites. SlmA may thus represent a special subclass of TetR-like proteins that have adapted conformational changes normally associated with inducer sensing in order to modulate an interaction with a partner protein. In this case, the adaptation ensures that SlmA only blocks cytokinesis in regions of the cell occupied by the origin-proximal portion of the chromosome where SlmA-binding sites are enriched. |
| first_indexed | 2024-12-23T05:03:11Z |
| format | Article |
| id | doaj.art-36bbe34080804605947d60742af5c206 |
| institution | Directory Open Access Journal |
| issn | 1553-7390 1553-7404 |
| language | English |
| last_indexed | 2024-12-23T05:03:11Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Genetics |
| spelling | doaj.art-36bbe34080804605947d60742af5c2062022-12-21T17:59:10ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042013-01-0192e100330410.1371/journal.pgen.1003304Identification of the SlmA active site responsible for blocking bacterial cytokinetic ring assembly over the chromosome.Hongbaek ChoThomas G BernhardtBacterial cells use chromosome-associated division inhibitors to help coordinate the processes of DNA replication and segregation with cytokinesis. SlmA from Escherichia coli, a member of the tetracycline repressor (TetR)-like protein family, is one example of this class of regulator. It blocks the assembly of the bacterial cytokinetic ring by interfering with the polymerization of the tubulin-like FtsZ protein in a manner that is dramatically stimulated upon specific DNA binding. Here we used a combination of molecular genetics and biochemistry to identify the active site of SlmA responsible for disrupting FtsZ polymerization. Interestingly, this site maps to a region of SlmA that in the published DNA-free structure is partially occluded by the DNA-binding domains. In this conformation, the SlmA structure resembles the drug/inducer-bound conformers of other TetR-like proteins, which in the absence of inducer require an inward rotation of their DNA-binding domains to bind successive major grooves on operator DNA. Our results are therefore consistent with a model in which DNA-binding activates SlmA by promoting a rotational movement of the DNA-binding domains that fully exposes the FtsZ-binding sites. SlmA may thus represent a special subclass of TetR-like proteins that have adapted conformational changes normally associated with inducer sensing in order to modulate an interaction with a partner protein. In this case, the adaptation ensures that SlmA only blocks cytokinesis in regions of the cell occupied by the origin-proximal portion of the chromosome where SlmA-binding sites are enriched.http://europepmc.org/articles/PMC3573117?pdf=render |
| spellingShingle | Hongbaek Cho Thomas G Bernhardt Identification of the SlmA active site responsible for blocking bacterial cytokinetic ring assembly over the chromosome. PLoS Genetics |
| title | Identification of the SlmA active site responsible for blocking bacterial cytokinetic ring assembly over the chromosome. |
| title_full | Identification of the SlmA active site responsible for blocking bacterial cytokinetic ring assembly over the chromosome. |
| title_fullStr | Identification of the SlmA active site responsible for blocking bacterial cytokinetic ring assembly over the chromosome. |
| title_full_unstemmed | Identification of the SlmA active site responsible for blocking bacterial cytokinetic ring assembly over the chromosome. |
| title_short | Identification of the SlmA active site responsible for blocking bacterial cytokinetic ring assembly over the chromosome. |
| title_sort | identification of the slma active site responsible for blocking bacterial cytokinetic ring assembly over the chromosome |
| url | http://europepmc.org/articles/PMC3573117?pdf=render |
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