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

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Flexibility of KorA, a plasmid-encoded, global transcription regulator, in the presence and the absence of its operator. / Rajasekar, Karthik; Lovering, Andrew; Dancea, Felician; Scott, David; Harris, Sarah ; Bingle, LE; Rosessle, Manfred; Thomas, Christopher; Hyde, Eva; White, Scott.

In: Nucleic Acids Research, Vol. 44, No. 10, 02.06.2016, p. 4947-4956.

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@article{d5f561545b7d451e9d1fbded8a2d6115,
title = "Flexibility of KorA, a plasmid-encoded, global transcription regulator, in the presence and the absence of its operator",
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 co-operatively. 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-aminoacid subunits, folding into an N-terminal DNA-binding domain and a C-terminal dimerisation 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, NMR 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 co-operative binding to KorB. Unexpectedly, the C-terminal domain of KorA is structurally similar to the dimerisation domain of the tumour suppressor p53.",
author = "Karthik Rajasekar and Andrew Lovering and Felician Dancea and David Scott and Sarah Harris and LE Bingle and Manfred Rosessle and Christopher Thomas and Eva Hyde and Scott White",
year = "2016",
month = jun,
day = "2",
doi = "10.1093/nar/gkw191",
language = "English",
volume = "44",
pages = "4947--4956",
journal = "Nucleic Acids Research",
issn = "0305-1048",
publisher = "Oxford University Press",
number = "10",

}

RIS

TY - JOUR

T1 - Flexibility of KorA, a plasmid-encoded, global transcription regulator, in the presence and the absence of its operator

AU - Rajasekar, Karthik

AU - Lovering, Andrew

AU - Dancea, Felician

AU - Scott, David

AU - Harris, Sarah

AU - Bingle, LE

AU - Rosessle, Manfred

AU - Thomas, Christopher

AU - Hyde, Eva

AU - White, Scott

PY - 2016/6/2

Y1 - 2016/6/2

N2 - 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 co-operatively. 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-aminoacid subunits, folding into an N-terminal DNA-binding domain and a C-terminal dimerisation 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, NMR 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 co-operative binding to KorB. Unexpectedly, the C-terminal domain of KorA is structurally similar to the dimerisation domain of the tumour suppressor p53.

AB - 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 co-operatively. 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-aminoacid subunits, folding into an N-terminal DNA-binding domain and a C-terminal dimerisation 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, NMR 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 co-operative binding to KorB. Unexpectedly, the C-terminal domain of KorA is structurally similar to the dimerisation domain of the tumour suppressor p53.

U2 - 10.1093/nar/gkw191

DO - 10.1093/nar/gkw191

M3 - Article

VL - 44

SP - 4947

EP - 4956

JO - Nucleic Acids Research

JF - Nucleic Acids Research

SN - 0305-1048

IS - 10

ER -