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

Rajasekar, K V, Lovering, A L, Dancea, F, Scott, D J, Harris, S A, Bingle, Lewis, Roessle, M, Thomas, C M, Hyde, E I and White, S A (2016) Flexibility of KorA, a plasmid-encoded, global transcription regulator, in the presence and the absence of its operator. Nucleic Acids Research, 1. ISSN 0305-1048

Nucl. Acids Res.-2016-Rajasekar-nar_gkw191.pdf

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The IncP (Incompatibility group P) plasmids are im-
portant carriers in the spread of antibiotic resis-
tance across Gram-negative bacteria. Gene expres-
sion 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 vary-
ing 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 sub-
units, folding into an N-terminal DNA-binding do-
main 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 con-
sensus 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
Additional Information: This article has been accepted for publication in Nucleic Acids Research Published by Oxford University Press.
Subjects: Sciences
Divisions: Faculty of Applied Sciences
Faculty of Applied Sciences > Department of Pharmacy Health and Wellbeing
Health Sciences and Wellbeing Beacon
Depositing User: Paula Normington
Date Deposited: 30 Mar 2016 13:42
Last Modified: 20 Sep 2017 01:58
URI: http://sure.sunderland.ac.uk/id/eprint/6131

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