Data from: The β-D-manno-heptoses are immune agonists across kingdoms
Data files
Jul 26, 2024 version files 176.29 KB
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Archaeal__HENase_alignments.fas
14.04 KB
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Eukaryotic__HENase_alignments.fas
15.66 KB
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Fig_2G.xlsx
9.67 KB
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Fig_3A_.xlsx
10.72 KB
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Fig_4E_.xlsx
11.43 KB
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Fig_4F.xlsx
17.78 KB
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Fig_S14_.xlsx
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Fig._S16C.xlsx
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Fig.S10B.xlsx
10.77 KB
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Fig.S11D.xlsx
9.78 KB
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Fig.S12.xlsx
10.63 KB
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Fig.S13.xlsx
10.78 KB
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Fig.S9.xlsx
19.48 KB
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README.md
2.40 KB
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Tree_of__archaeal_HENases.nwk
966 B
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Tree_of__eukaryotic_HENases.nwk
1.11 KB
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Tree_of_viral_HENases.nwk
574 B
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viral_HENase_alignments.fas
9.03 KB
Abstract
Bacterial small molecule metabolites such as adenosine-diphosphate-D-glycero-β-D-manno-heptose (ADP-heptose) and their derivatives act as effective innate immune agonists in mammals. We showed that functional nucleotide-diphosphate-heptose biosynthetic enzymes (HBEs) are distributed widely in bacteria, archaea, eukaryotes, and viruses. We identified a conserved STTR5 motif as a hallmark of heptose nucleotidyltransferases that can synthesize not only ADP-heptose but also cytidine-diphosphate (CDP)- and uridine-diphosphate (UDP)-heptose. Both CDP- and UDP-heptoses are agonists that trigger stronger alpha-protein kinase 1 (ALPK1)-dependent immune responses than ADP-heptose in human and mouse cells and mice. We also produced ADP-heptose in archaea and verified its innate immune agonist functions. Hence, the β-D-manno-heptoses are cross-kingdom small molecule pathogen-associated molecular patterns that activate the ALPK1-dependent innate immune signaling cascade.
Paper: The β-D-manno-heptoses are immune agonists across kingdoms
[Access this dataset on Dryad]( https://doi.org/10.5061/dryad.rr4xgxdgs)
Descriptions
This folder contains the enzymatic assay data of NDP-heptose biosynthetic enzymes (HBEs) data, phylogenesis of HBEs performing nucleotidyltransferase activities (HENases) beyond bacteria, source data of cytokines in mice, qPCR source data, and dual luciferase assay data.
Enzymatic assay data of HBEs
NDP-heptoses generated by HENases combined with appropriate HBEs in four-step reactions (Fig. 2G).
Synthesis of NDP-heptoses by different HBE combinations at a simulated physiological condition (pH 7.2, S7P 0.1 mM, ATP 3.5 mM, CTP 0.3 mM, and UTP 0.7 mM) (Fig. 3A).
Phylogenesis
Three .fasta files and three .nwk files were contained.
The “Viral HENase aligments.fas”, “Archaeal HENase aligments.fas”, “Eukaryotic HENase aligments.fas” contain the aligned sequences of representative HENases from viruses, archaea, and eukaryota, respectively. Three phylogenetic trees were generated by MEGA 6 using the aligned sequences and formed the following files: “Tree of viral HENase.nwk”, “Tree of archaeal HENase.nwk”, “Tree of eukaryotic HENase.nwk”.
Source data of cytokines in mice
Cytokine concentrations in the serum of wild-type (WT) and Alpk1−/− mice injected with ADP-, CDP-, or UDP-heptose intravenously (Fig. 4F and Fig. S13 ).
Cytokine concentrations in the lungs of WT or Alpk1−/− mice infected with Burkholderia multivorans ATCC BAA-247 intranasally (Fig. S14).
qPCR source data
qPCR source data of IP-10 expression in BMDM cells upon the incubation of ADP-, CDP-, or UDP-heptose (Fig. S9).
Source data of NF-kB luciferase assays
ADP-, CDP-, or UDP-heptose triggered NF-κB activation in 293T cell or its ALPK1−/− mutant (Fig.4E).
Electroporation of ADP-, CDP-, or UDP-heptose into 293T cells (Fig. S10B).
NF-κB activation triggered by the cell lysates of Methanococcus maripaludis 01 in 293T cell or its ALPK1−/− mutant (Fig. S11D).
Assessments of possible interactive effects among ADP-, CDP-, and UDP-heptoses via NF-κB-driven luciferase assays (Fig. S12).
Assessments of ADP-heptose triggered NF-κB activation in 293T ALPK1−/−cells expressing varied ALPK1 homologues (Fig.S16C).