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Title: A novel transcriptional regulator of L-arabinose utilization in human gut bacteria

Abstract

Carbohydrate metabolism plays a crucial role in the ecophysiology of human gut microbiota. Mechanisms of transcriptional regulation of sugar catabolism in commensal and prevalent human gut bacteria such as Bacteroides thetaiotaomicron remain mostly unknown. By a combination of bioinformatics and experimental approaches, we have identified an NrtR family transcription factor (BT0354 in B. thetaiotaomicron, BtAraR) as a novel regulator controlling the arabinose utilization genes. L-arabinose was confirmed to be a negative effector of BtAraR. We have solved the crystal structures of the apo and L-arabinose-bound BtAraR proteins, as well as the complex of apo-protein with a specific DNA operator. BtAraR forms a homodimer with each subunit comprised of the ligand-binding Nudix hydrolase-like domain and the DNA-binding winged-helix-turn-helix (wHTH) domain. We have identified the residues involved in binding of L-arabinose and recognition of DNA. The majority of these residues are well conserved in the AraR orthologs in Bacteroidetes. In the structure of the BtAraR-DNA complex, we found the unique interaction of arginine intercalating its guanidinum moiety into the base pair stacking of B-DNA. L-arabinose binding induces movement of wHTH domains, resulting in a conformation unsuitable for DNA binding. Our analysis facilitates reconstruction of the metabolic and regulatory networks involved in carbohydratemore » utilization in human gut Bacteroides.« less

Authors:
; ; ; ; ;
Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States)
Sponsoring Org.:
National Institutes of Health (NIH); USDOE Office of Science - Office of Biological and Environmental Research; Russian Science Foundation
OSTI Identifier:
1391924
DOE Contract Number:  
AC02-06CH11357
Resource Type:
Journal Article
Journal Name:
Nucleic Acids Research
Additional Journal Information:
Journal Volume: 43; Journal Issue: 21; Journal ID: ISSN 0305-1048
Publisher:
Oxford University Press
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; 59 BASIC BIOLOGICAL SCIENCES

Citation Formats

Chang, Changsoo, Tesar, Christine, Li, Xiaoqing, Kim, Youngchang, Rodionov, Dmitry A., and Joachimiak, Andrzej. A novel transcriptional regulator of L-arabinose utilization in human gut bacteria. United States: N. p., 2015. Web. doi:10.1093/nar/gkv1005.
Chang, Changsoo, Tesar, Christine, Li, Xiaoqing, Kim, Youngchang, Rodionov, Dmitry A., & Joachimiak, Andrzej. A novel transcriptional regulator of L-arabinose utilization in human gut bacteria. United States. doi:10.1093/nar/gkv1005.
Chang, Changsoo, Tesar, Christine, Li, Xiaoqing, Kim, Youngchang, Rodionov, Dmitry A., and Joachimiak, Andrzej. Sun . "A novel transcriptional regulator of L-arabinose utilization in human gut bacteria". United States. doi:10.1093/nar/gkv1005.
@article{osti_1391924,
title = {A novel transcriptional regulator of L-arabinose utilization in human gut bacteria},
author = {Chang, Changsoo and Tesar, Christine and Li, Xiaoqing and Kim, Youngchang and Rodionov, Dmitry A. and Joachimiak, Andrzej},
abstractNote = {Carbohydrate metabolism plays a crucial role in the ecophysiology of human gut microbiota. Mechanisms of transcriptional regulation of sugar catabolism in commensal and prevalent human gut bacteria such as Bacteroides thetaiotaomicron remain mostly unknown. By a combination of bioinformatics and experimental approaches, we have identified an NrtR family transcription factor (BT0354 in B. thetaiotaomicron, BtAraR) as a novel regulator controlling the arabinose utilization genes. L-arabinose was confirmed to be a negative effector of BtAraR. We have solved the crystal structures of the apo and L-arabinose-bound BtAraR proteins, as well as the complex of apo-protein with a specific DNA operator. BtAraR forms a homodimer with each subunit comprised of the ligand-binding Nudix hydrolase-like domain and the DNA-binding winged-helix-turn-helix (wHTH) domain. We have identified the residues involved in binding of L-arabinose and recognition of DNA. The majority of these residues are well conserved in the AraR orthologs in Bacteroidetes. In the structure of the BtAraR-DNA complex, we found the unique interaction of arginine intercalating its guanidinum moiety into the base pair stacking of B-DNA. L-arabinose binding induces movement of wHTH domains, resulting in a conformation unsuitable for DNA binding. Our analysis facilitates reconstruction of the metabolic and regulatory networks involved in carbohydrate utilization in human gut Bacteroides.},
doi = {10.1093/nar/gkv1005},
journal = {Nucleic Acids Research},
issn = {0305-1048},
number = 21,
volume = 43,
place = {United States},
year = {2015},
month = {10}
}

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    Works referencing / citing this record:

    Glycan utilisation system in Bacteroides and Bifidobacteria and their roles in gut stability and health
    journal, July 2019