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Structure of Bacteroides thetaiotaomicron BT2081 at 2.05?A resolution: the first structural representative of a new protein family that may play a role in carbohydrate metabolism.

ABSTRACT: BT2081 from Bacteroides thetaiotaomicron (GenBank accession code NP_810994.1) is a member of a novel protein family consisting of over 160 members, most of which are found in the different classes of Bacteroidetes. Genome-context analysis lends support to the involvement of this family in carbohydrate metabolism, which plays a key role in B. thetaiotaomicron as a predominant bacterial symbiont in the human distal gut microbiome. The crystal structure of BT2081 at 2.05?Å resolution represents the first structure from this new protein family. BT2081 consists of an N-terminal domain, which adopts a ?-sandwich immunoglobulin-like fold, and a larger C-terminal domain with a ?-sandwich jelly-roll fold. Structural analyses reveal that both domains are similar to those found in various carbohydrate-active enzymes. The C-terminal ?-jelly-roll domain contains a potential carbohydrate-binding site that is highly conserved among BT2081 homologs and is situated in the same location as the carbohydrate-binding sites that are found in structurally similar glycoside hydrolases (GHs). However, in BT2081 this site is partially occluded by surrounding loops, which results in a deep solvent-accessible pocket rather than a shallower solvent-exposed cleft.

SUBMITTER: Yeh AP

PROVIDER: S-EPMC2954218 | biostudies-literature | 2010 Oct

REPOSITORIES: biostudies-literature

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Structure of Bacteroides thetaiotaomicron BT2081 at 2.05 Å resolution: the first structural representative of a new protein family that may play a role in carbohydrate metabolism.

Yeh Andrew P AP Abdubek Polat P Astakhova Tamara T Axelrod Herbert L HL Bakolitsa Constantina C Cai Xiaohui X Carlton Dennis D Chen Connie C Chiu Hsiu Ju HJ Chiu Michelle M Clayton Thomas T Das Debanu D Deller Marc C MC Duan Lian L Ellrott Kyle K Farr Carol L CL Feuerhelm Julie J Grant Joanna C JC Grzechnik Anna A Han Gye Won GW Jaroszewski Lukasz L Jin Kevin K KK Klock Heath E HE Knuth Mark W MW Kozbial Piotr P Krishna S Sri SS Kumar Abhinav A Lam Winnie W WW Marciano David D McMullan Daniel D Miller Mitchell D MD Morse Andrew T AT Nigoghossian Edward E Nopakun Amanda A Okach Linda L Puckett Christina C Reyes Ron R Tien Henry J HJ Trame Christine B CB van den Bedem Henry H Weekes Dana D Wooten Tiffany T Xu Qingping Q Hodgson Keith O KO Wooley John J Elsliger Marc André MA Deacon Ashley M AM Godzik Adam A Lesley Scott A SA Wilson Ian A IA

Acta crystallographica. Section F, Structural biology and crystallization communications 20100804 Pt 10

BT2081 from Bacteroides thetaiotaomicron (GenBank accession code NP_810994.1) is a member of a novel protein family consisting of over 160 members, most of which are found in the different classes of Bacteroidetes. Genome-context analysis lends support to the involvement of this family in carbohydrate metabolism, which plays a key role in B. thetaiotaomicron as a predominant bacterial symbiont in the human distal gut microbiome. The crystal structure of BT2081 at 2.05 Å resolution represents the ...[more]

PMID: 20944224

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Project description:Thiamine (vitamin B1) is an essential cofactor for all organisms. Humans primarily acquire thiamine through their diet, and thiamine deficiencies have adverse neurological effects. However, the role gut microbes play in modulating thiamine availability is poorly understood, and little is known about how thiamine impacts the stability of microbial gut communities. To investigate thiamine's role in the gut, we utilized the model gut microbe Bacteroides thetaiotaomicron. Transcriptome sequencing (RNA-seq) revealed a global downregulation of thiamine and amino acid biosynthesis, glycolysis, and purine metabolism when thiamine was present. Using genetic mutants with thiamine biosynthesis and transport locus mutations, we determined both systems were critical for growth in thiamine-deficient medium. The defect in the double transport mutant suggests an uncharacterized feedback mechanism between thiamine transport and biosynthesis in B. thetaiotaomicron. Mutant phenotypes were recapitulated during pairwise competitions, reinforcing the importance of encoding versatile thiamine acquisition mechanisms when thiamine concentrations are variable. In addition, liquid chromatography-mass spectrometry (LC-MS) analyses corroborate that exogenous thiamine levels affect the internal thiamine pool of B. thetaiotaomicron. Furthermore, we computationally examined the ability of other gut microbes to acquire thiamine and identified lineage-specific differences in thiamine acquisition strategies. Among the Bacteroidetes, the capacities for both thiamine transport and biosynthesis are common. Together, these data show that thiamine acquisition mechanisms used by B. thetaiotaomicron not only are critical for its physiology and fitness but also provide the opportunity to model how other gut microbes may respond to the shifting availability of thiamine in the gut. IMPORTANCE Variation in the ability of gut microbes to transport, synthesize, and compete for vitamin B1 (thiamine) is expected to impact the structure and stability of the microbiota, and ultimately this variation may have both direct and indirect effects on human health. Our study identifies the diverse strategies employed by gut Bacteroidetes to acquire thiamine. We demonstrate how the presence or absence of thiamine biosynthesis or transport dramatically affects the abundance of B. thetaiotaomicron in a competitive environment. This study adds further evidence that altering the presence or concentrations of water-soluble vitamins such as thiamine may be an effective method for manipulating gut community composition. In turn, targeted thiamine delivery could be used therapeutically to alter dysbiotic communities linked to disease. Author Video: An author video summary of this article is available.

Project description:Microbial colonization of the mammalian gut is largely ascribed to the ability to utilize nutrients available in that environment. To understand how beneficial microbes establish a relationship with their hosts, it is crucial to determine what other abilities promote gut colonization. We now report that colonization of the murine gut by the beneficial microbe Bacteroides thetaiotaomicron requires activation of a putative translation factor by the major transcriptional regulator of gut colonization and carbohydrate utilization. To ascertain how this regulator-called BT4338-promotes gut colonization, we identified BT4338-regulated genes and BT4338-bound DNA sequences. Unexpectedly, the gene whose expression was most reduced upon BT4338 inactivation was fusA2, specifying a putative translation factor. We determined that fusA2 activation by BT4338 is conserved in another Bacteroides species and essential for gut colonization in B. thetaiotaomicron because a mutant lacking the BT4338 binding site in the fusA2 promoter exhibited a colonization defect similar to that of a mutant lacking the fusA2 gene. Furthermore, we demonstrated that BT4338 promotes gut colonization independently of its role in carbohydrate utilization because the fusA2 gene was dispensable for utilization of carbohydrates that depend on BT4338 Our findings suggest that microbial gut colonization requires the use of alternative protein synthesis factors.IMPORTANCE The bacteria occupying the mammalian gut have evolved unique strategies to thrive in their environment. Bacteroides organisms, which often comprise 25 to 50% of the human gut microbiota, derive nutrients from structurally diverse complex polysaccharides, commonly called dietary fibers. This ability requires an expansive genetic repertoire that is coordinately regulated to achieve expression of those genes dedicated to utilizing only those dietary fibers present in the environment. Here we identify the global regulon of a transcriptional regulator necessary for dietary fiber utilization and gut colonization. We demonstrate that this transcription factor regulates hundreds of genes putatively involved in dietary fiber utilization as well as a putative translation factor dispensable for growth on such nutrients but necessary for survival in the gut. These findings suggest that gut bacteria coordinate cellular metabolism with protein synthesis via specialized translation factors to promote survival in the mammalian gut.

Dataset Information

Structure of Bacteroides thetaiotaomicron BT2081 at 2.05?A resolution: the first structural representative of a new protein family that may play a role in carbohydrate metabolism.

Publications

Structure of Bacteroides thetaiotaomicron BT2081 at 2.05 Å resolution: the first structural representative of a new protein family that may play a role in carbohydrate metabolism.

Similar Datasets

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