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

Abstract

We report that 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. Furthermore, our analysis facilitates reconstruction of the metabolic and regulatorymore » networks involved in carbohydrate utilization in human gut Bacteroides.« less

Authors:
 [1];  [1];  [2];  [1];  [3];  [4]
  1. Argonne National Lab. (ANL), Argonne, IL (United States)
  2. Sanford-Burnham Medical Research Institute, La Jolla, CA (United States)
  3. Sanford-Burnham Medical Research Institute, La Jolla, CA (United States); Russian Academy of Sciences, Moscow (Russia)
  4. Argonne National Lab. (ANL), Argonne, IL (United States); Univ. of Chicago, Chicago, IL (United States)
Publication Date:
Research Org.:
Argonne National Laboratory (ANL), Argonne, IL (United States)
Sponsoring Org.:
USDOE; National Institutes of Health (NIH); Russian Science Foundation
OSTI Identifier:
1261150
Grant/Contract Number:  
AC02-06CH11357; 14-14-00289; GM094585
Resource Type:
Journal Article: Accepted Manuscript
Journal Name:
Nucleic Acids Research
Additional Journal Information:
Journal Name: Nucleic Acids Research; Journal ID: ISSN 0305-1048
Publisher:
Oxford University Press
Country of Publication:
United States
Language:
English
Subject:
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. https://doi.org/10.1093/nar/gkv1005
Chang, Changsoo, Tesar, Christine, Li, Xiaoqing, Kim, Youngchang, Rodionov, Dmitry A., and Joachimiak, Andrzej. 2015. "A novel transcriptional regulator of L-arabinose utilization in human gut bacteria". United States. https://doi.org/10.1093/nar/gkv1005. https://www.osti.gov/servlets/purl/1261150.
@article{osti_1261150,
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 = {We report that 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. Furthermore, our analysis facilitates reconstruction of the metabolic and regulatory networks involved in carbohydrate utilization in human gut Bacteroides.},
doi = {10.1093/nar/gkv1005},
url = {https://www.osti.gov/biblio/1261150}, journal = {Nucleic Acids Research},
issn = {0305-1048},
number = ,
volume = ,
place = {United States},
year = {Sun Oct 04 00:00:00 EDT 2015},
month = {Sun Oct 04 00:00:00 EDT 2015}
}

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Works referenced in this record:

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Works referencing / citing this record:

Comparative Genomics Reveals the Regulatory Complexity of Bifidobacterial Arabinose and Arabino-Oligosaccharide Utilization
journal, April 2018


The effects of micronutrient deficiencies on bacterial species from the human gut microbiota
journal, May 2017


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


Regulation of alginate catabolism involves a GntR family repressor in the marine flavobacterium Zobellia galactanivorans DsijT
journal, June 2020


Comparative Genomics Reveals the Regulatory Complexity of Bifidobacterial Arabinose and Arabino-Oligosaccharide Utilization
journal, April 2018