Flexibility of KorA, a plasmid-encoded, global transcription regulator, in the presence and the absence of its operator

Rajasekar, Karthik V. and Lovering, Andrew L. and Dancea, Felician and Scott, David J. and Harris, Sarah A. and Bingle, Lewis E.H. and Roessle, Manfred and Thomas, Christopher M. and 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

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Abstract

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.

Item Type: Article
Schools/Departments: University of Nottingham, UK > Faculty of Science > School of Biosciences
Identification Number: 10.1093/nar/gkw191
Depositing User: Scott, David
Date Deposited: 21 Apr 2017 10:50
Last Modified: 21 Apr 2017 10:55
URI: http://eprints.nottingham.ac.uk/id/eprint/41960

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