The crystal structure of AcrR from Mycobacterium tuberculosis reveals a one‐component transcriptional regulation mechanism

Transcriptional regulator proteins are closely involved in essential survival strategies in bacteria. AcrR is a one‐component allosteric repressor of the genes associated with lipid transport and antibiotic resistance. When fatty acid ligands bind to the C‐terminal ligand‐binding cavity of AcrR, a c...

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Main Authors: Sung‐Min Kang, Do‐Hee Kim, Chenglong Jin, Hee‐Chul Ahn, Bong‐Jin Lee
Format: Article
Language:English
Published: Wiley 2019-10-01
Series:FEBS Open Bio
Subjects:
Online Access:https://doi.org/10.1002/2211-5463.12710
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author Sung‐Min Kang
Do‐Hee Kim
Chenglong Jin
Hee‐Chul Ahn
Bong‐Jin Lee
author_facet Sung‐Min Kang
Do‐Hee Kim
Chenglong Jin
Hee‐Chul Ahn
Bong‐Jin Lee
author_sort Sung‐Min Kang
collection DOAJ
description Transcriptional regulator proteins are closely involved in essential survival strategies in bacteria. AcrR is a one‐component allosteric repressor of the genes associated with lipid transport and antibiotic resistance. When fatty acid ligands bind to the C‐terminal ligand‐binding cavity of AcrR, a conformational change in the N‐terminal operator‐binding region of AcrR is triggered, which releases the repressed DNA and initiates transcription. This paper focuses on the structural transition mechanism of AcrR of Mycobacterium tuberculosis upon DNA and ligand binding. AcrR loses its structural integrity upon ligand‐mediated structural alteration and bends toward the promoter DNA in a more compact form, initiating a rotational motion. Our functional characterization of AcrR and description of the ligand‐ and DNA‐recognition mechanism may facilitate the discovery of new therapies for tuberculosis.
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spelling doaj-art-0bc95aa3dd404d97948eb4f5e1ee19d62024-12-06T11:26:04ZengWileyFEBS Open Bio2211-54632019-10-019101713172510.1002/2211-5463.12710The crystal structure of AcrR from Mycobacterium tuberculosis reveals a one‐component transcriptional regulation mechanismSung‐Min Kang0Do‐Hee Kim1Chenglong Jin2Hee‐Chul Ahn3Bong‐Jin Lee4The Research Institute of Pharmaceutical Sciences, College of Pharmacy Seoul National University Seoul KoreaThe Research Institute of Pharmaceutical Sciences, College of Pharmacy Seoul National University Seoul KoreaThe Research Institute of Pharmaceutical Sciences, College of Pharmacy Seoul National University Seoul KoreaDepartment of Pharmacy Dongguk University‐Seoul Ilsandong‐gu Goyang KoreaThe Research Institute of Pharmaceutical Sciences, College of Pharmacy Seoul National University Seoul KoreaTranscriptional regulator proteins are closely involved in essential survival strategies in bacteria. AcrR is a one‐component allosteric repressor of the genes associated with lipid transport and antibiotic resistance. When fatty acid ligands bind to the C‐terminal ligand‐binding cavity of AcrR, a conformational change in the N‐terminal operator‐binding region of AcrR is triggered, which releases the repressed DNA and initiates transcription. This paper focuses on the structural transition mechanism of AcrR of Mycobacterium tuberculosis upon DNA and ligand binding. AcrR loses its structural integrity upon ligand‐mediated structural alteration and bends toward the promoter DNA in a more compact form, initiating a rotational motion. Our functional characterization of AcrR and description of the ligand‐ and DNA‐recognition mechanism may facilitate the discovery of new therapies for tuberculosis.https://doi.org/10.1002/2211-5463.12710AcrRMycobacterium tuberculosistranscriptional regulatorX‐ray crystallography
spellingShingle Sung‐Min Kang
Do‐Hee Kim
Chenglong Jin
Hee‐Chul Ahn
Bong‐Jin Lee
The crystal structure of AcrR from Mycobacterium tuberculosis reveals a one‐component transcriptional regulation mechanism
FEBS Open Bio
AcrR
Mycobacterium tuberculosis
transcriptional regulator
X‐ray crystallography
title The crystal structure of AcrR from Mycobacterium tuberculosis reveals a one‐component transcriptional regulation mechanism
title_full The crystal structure of AcrR from Mycobacterium tuberculosis reveals a one‐component transcriptional regulation mechanism
title_fullStr The crystal structure of AcrR from Mycobacterium tuberculosis reveals a one‐component transcriptional regulation mechanism
title_full_unstemmed The crystal structure of AcrR from Mycobacterium tuberculosis reveals a one‐component transcriptional regulation mechanism
title_short The crystal structure of AcrR from Mycobacterium tuberculosis reveals a one‐component transcriptional regulation mechanism
title_sort crystal structure of acrr from mycobacterium tuberculosis reveals a one component transcriptional regulation mechanism
topic AcrR
Mycobacterium tuberculosis
transcriptional regulator
X‐ray crystallography
url https://doi.org/10.1002/2211-5463.12710
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