AI Article Synopsis
- * A conserved protein motif identified in various organisms indicates that certain enzymes can synthesize ADP-heptose, CDP-heptose, and UDP-heptose, with the latter two triggering stronger immune responses.
- * The study demonstrates that β-d-heptoses are significant, cross-kingdom molecules that activate the ALPK1-dependent immune signaling pathway, highlighting their role as pathogen-associated molecular patterns.
Article Abstract
Bacterial small molecule metabolites such as adenosine-diphosphate-d--β-d--heptose (ADP-heptose) and their derivatives act as effective innate immune agonists in mammals. We show that functional nucleotide-diphosphate-heptose biosynthetic enzymes (HBEs) are distributed widely in bacteria, archaea, eukaryotes, and viruses. We identified a conserved STT 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--heptoses are cross-kingdom, small-molecule, pathogen-associated molecular patterns that activate the ALPK1-dependent innate immune signaling cascade.
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| http://dx.doi.org/10.1126/science.adk7314 | DOI Listing |
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