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Solution NMR structure of the helicase associated domain BVU_0683(627-691) from Bacteroides vulgatus provides first structural coverage for protein domain family PF03457 and indicates domain binding to DNA.

ABSTRACT: A high-quality NMR structure of the helicase associated (HA) domain comprising residues 627-691 of the 753-residue protein BVU_0683 from Bacteroides vulgatus exhibits an all ?-helical fold. The structure presented here is the first representative for the large protein domain family PF03457 (currently 742 members) of HA domains. Comparison with structurally similar proteins supports the hypothesis that HA domains bind to DNA and that binding specificity varies greatly within the family of HA domains constituting PF03457.

SUBMITTER: Mills JL

PROVIDER: S-EPMC3637686 | biostudies-literature | 2013 Mar

REPOSITORIES: biostudies-literature

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Solution NMR structure of the helicase associated domain BVU_0683(627-691) from Bacteroides vulgatus provides first structural coverage for protein domain family PF03457 and indicates domain binding to DNA.

Mills Jeffrey L JL Acton Thomas B TB Xiao Rong R Everett John K JK Montelione Gaetano T GT Szyperski Thomas T

Journal of structural and functional genomics 20121116 1

A high-quality NMR structure of the helicase associated (HA) domain comprising residues 627-691 of the 753-residue protein BVU_0683 from Bacteroides vulgatus exhibits an all α-helical fold. The structure presented here is the first representative for the large protein domain family PF03457 (currently 742 members) of HA domains. Comparison with structurally similar proteins supports the hypothesis that HA domains bind to DNA and that binding specificity varies greatly within the family of HA doma ...[more]

PMID: 23160728

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Project description:BackgroundImmune checkpoint blockade (ICB) shows lasting benefits in advanced melanoma; however, not all patients respond to this treatment and many develop potentially life-threatening immune-related adverse events (irAEs). Identifying individuals who will develop irAEs is critical in order to improve the quality of care. Here, we prospectively demonstrate that the gut microbiome predicts irAEs in melanoma patients undergoing ICB.MethodsPre-, during, and post-treatment stool samples were collected from 27 patients with advanced stage melanoma treated with IPI (anti-CTLA-4) and NIVO (anti-PD1) ICB inhibitors at NYU Langone Health. We completed 16S rRNA gene amplicon sequencing, DNA deep shotgun metagenomic, and RNA-seq metatranscriptomic sequencing. The divisive amplicon denoising algorithm (DADA2) was used to process 16S data. Taxonomy for shotgun sequencing data was assigned using MetaPhlAn2, and gene pathways were assigned using HUMAnN 2.0. Compositionally aware differential expression analysis was performed using ANCOM. The Cox-proportional hazard model was used to assess the prospective role of the gut microbiome (GMB) in irAES, with adjustment for age, sex, BMI, immune ICB treatment type, and sequencing batch.ResultsTwo natural GMB clusters with distinct community compositions were identified from the analysis of 16S rRNA data (R2 = 0.16, p < 0.001). In Cox-proportional hazard modeling, these two clusters showed a near 7-fold differential risk for developing irAEs within 1 year of initiating treatment (HR = 6.89 [95% CI: 1.33-35.58]). Using shotgun metagenomics, we further identified 37 bacterial strains differentially expressed between the risk groups, with specific dominance of Bacteroides dorei within the high-risk GMB cluster and Bacteroides vulgatus in the low-risk cluster. The high-risk cluster also appeared to have elevated expression of several functional pathways, including those associated with adenosine metabolism (all FDR < 0.05). A sub-analysis of samples (n = 10 participants) at baseline and 6 and 12 weeks after the start of treatment revealed that the microbiome remained stable over the course of treatment (R2 = 0.88, p < 0.001).ConclusionsWe identified two distinct fecal bacterial community clusters which are associated differentially with irAEs in ICB-treated advanced melanoma patients.

Dataset Information

Solution NMR structure of the helicase associated domain BVU_0683(627-691) from Bacteroides vulgatus provides first structural coverage for protein domain family PF03457 and indicates domain binding to DNA.

Publications

Solution NMR structure of the helicase associated domain BVU_0683(627-691) from Bacteroides vulgatus provides first structural coverage for protein domain family PF03457 and indicates domain binding to DNA.

Similar Datasets

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