Flexibility of KorA, a plasmid-encoded, global transcription regulator, in the presence and the absence of its operator
The IncP (Incompatibility group P) plasmids are important carriers in the spread of antibiotic resistance across Gram-negative bacteria. Gene expression in the IncP-1 plasmids is stringently controlled by a network of four global repressors, KorA, KorB, TrbA and KorC interacting cooperatively. Intri...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
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Oxford University Press
2016
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| Online Access: | https://eprints.nottingham.ac.uk/41960/ |
| _version_ | 1848796389970018304 |
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| author | Rajasekar, Karthik V. Lovering, Andrew L. Dancea, Felician Scott, David J. Harris, Sarah A. Bingle, Lewis E.H. Roessle, Manfred Thomas, Christopher M. Hyde, Eva I. White, Scott A. |
| author_facet | Rajasekar, Karthik V. Lovering, Andrew L. Dancea, Felician Scott, David J. Harris, Sarah A. Bingle, Lewis E.H. Roessle, Manfred Thomas, Christopher M. Hyde, Eva I. White, Scott A. |
| author_sort | Rajasekar, Karthik V. |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | The IncP (Incompatibility group P) plasmids are important carriers in the spread of antibiotic resistance across Gram-negative bacteria. Gene expression in the IncP-1 plasmids is stringently controlled by a network of four global repressors, KorA, KorB, TrbA and KorC interacting cooperatively. Intriguingly, KorA and KorB can act as co-repressors at varying distances between their operators, even when they are moved to be on opposite sides of the DNA. KorA is a homodimer with the 101-amino acid subunits, folding into an N-terminal DNA-binding domain and a C-terminal dimerization domain. In this study, we have determined the structures of the free KorA repressor and two complexes each bound to a 20-bp palindromic DNA duplex containing its consensus operator sequence. Using a combination of X-ray crystallography, nuclear magnetic resonance spectroscopy, SAXS and molecular dynamics calculations, we show that the linker between the two domains is very flexible and the protein remains highly mobile in the presence of DNA. This flexibility allows the DNA-binding domains of the dimer to straddle the operator DNA on binding and is likely to be important in cooperative binding to KorB. Unexpectedly, the C-terminal domain of KorA is structurally similar to the dimerization domain of the tumour suppressor p53. |
| first_indexed | 2025-11-14T19:47:13Z |
| format | Article |
| id | nottingham-41960 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| last_indexed | 2025-11-14T19:47:13Z |
| publishDate | 2016 |
| publisher | Oxford University Press |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-419602020-05-04T17:40:35Z https://eprints.nottingham.ac.uk/41960/ Flexibility of KorA, a plasmid-encoded, global transcription regulator, in the presence and the absence of its operator Rajasekar, Karthik V. Lovering, Andrew L. Dancea, Felician Scott, David J. Harris, Sarah A. Bingle, Lewis E.H. Roessle, Manfred Thomas, Christopher M. Hyde, Eva I. White, Scott A. The IncP (Incompatibility group P) plasmids are important carriers in the spread of antibiotic resistance across Gram-negative bacteria. Gene expression in the IncP-1 plasmids is stringently controlled by a network of four global repressors, KorA, KorB, TrbA and KorC interacting cooperatively. Intriguingly, KorA and KorB can act as co-repressors at varying distances between their operators, even when they are moved to be on opposite sides of the DNA. KorA is a homodimer with the 101-amino acid subunits, folding into an N-terminal DNA-binding domain and a C-terminal dimerization domain. In this study, we have determined the structures of the free KorA repressor and two complexes each bound to a 20-bp palindromic DNA duplex containing its consensus operator sequence. Using a combination of X-ray crystallography, nuclear magnetic resonance spectroscopy, SAXS and molecular dynamics calculations, we show that the linker between the two domains is very flexible and the protein remains highly mobile in the presence of DNA. This flexibility allows the DNA-binding domains of the dimer to straddle the operator DNA on binding and is likely to be important in cooperative binding to KorB. Unexpectedly, the C-terminal domain of KorA is structurally similar to the dimerization domain of the tumour suppressor p53. Oxford University Press 2016-03-25 Article PeerReviewed Rajasekar, Karthik V., Lovering, Andrew L., Dancea, Felician, Scott, David J., Harris, Sarah A., Bingle, Lewis E.H., Roessle, Manfred, Thomas, Christopher M., Hyde, Eva I. and White, Scott A. (2016) Flexibility of KorA, a plasmid-encoded, global transcription regulator, in the presence and the absence of its operator. Nucleic Acids Research, 44 (10). pp. 4947-4956. ISSN 1362-4962 https://academic.oup.com/nar/article-lookup/doi/10.1093/nar/gkw191 doi:10.1093/nar/gkw191 doi:10.1093/nar/gkw191 |
| spellingShingle | Rajasekar, Karthik V. Lovering, Andrew L. Dancea, Felician Scott, David J. Harris, Sarah A. Bingle, Lewis E.H. Roessle, Manfred Thomas, Christopher M. Hyde, Eva I. White, Scott A. Flexibility of KorA, a plasmid-encoded, global transcription regulator, in the presence and the absence of its operator |
| title | Flexibility of KorA, a plasmid-encoded, global transcription regulator, in the presence and the absence of its operator |
| title_full | Flexibility of KorA, a plasmid-encoded, global transcription regulator, in the presence and the absence of its operator |
| title_fullStr | Flexibility of KorA, a plasmid-encoded, global transcription regulator, in the presence and the absence of its operator |
| title_full_unstemmed | Flexibility of KorA, a plasmid-encoded, global transcription regulator, in the presence and the absence of its operator |
| title_short | Flexibility of KorA, a plasmid-encoded, global transcription regulator, in the presence and the absence of its operator |
| title_sort | flexibility of kora, a plasmid-encoded, global transcription regulator, in the presence and the absence of its operator |
| url | https://eprints.nottingham.ac.uk/41960/ https://eprints.nottingham.ac.uk/41960/ https://eprints.nottingham.ac.uk/41960/ |