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

Journal Article · · Nucleic Acids Research
DOI:https://doi.org/10.1093/nar/gkv1005· OSTI ID:1261150
 [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)
+ Show Author Affiliations

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.

Research Organization:
Argonne National Laboratory (ANL), Argonne, IL (United States)
Sponsoring Organization:
USDOE; National Institutes of Health (NIH); Russian Science Foundation
Grant/Contract Number:
AC02-06CH11357; 14-14-00289; GM094585
OSTI ID:
1261150
Journal Information:
Nucleic Acids Research, Journal Name: Nucleic Acids Research; ISSN 0305-1048
Publisher:
Oxford University PressCopyright Statement
Country of Publication:
United States
Language:
English
Citation Metrics:
Cited by: 21 works
Citation information provided by
Web of Science

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Cited By (5)

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
Analysis of Temporal Changes in Growth and Gene Expression for Commensal Gut Microbes in Response to the Polyphenol Naringenin journal January 2018
Regulation of alginate catabolism involves a GntR family repressor in the marine flavobacterium Zobellia galactanivorans DsijT journal June 2020

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