8ZD3

Crystal structure of ALPK1-N+K in complex with CDP-heptose

This is a non-PDB format compatible entry.

Summary for 8ZD3

• Entry DOI: 10.2210/pdb8zd3/pdb
• Descriptor: Alpha-protein kinase 1, CYTIDINE-5'-DIPHOSPHATE, (2R,3S,4S,5S,6R)-6-[(1S)-1,2-bis(oxidanyl)ethyl]oxane-2,3,4,5-tetrol, ... (6 entities in total)
• Functional Keywords: complex, angonist, pattern recognition receptor, immune system
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 4
• Total formula weight: 169842.63

Authors

She, Y.,Ding, J.J.,Shao, F. (deposition date: 2024-05-01, release date: 2025-05-07, Last modification date: 2025-11-19)

Primary citation

Tang, Y.,Tian, X.,Wang, M.,Cui, Y.,She, Y.,Shi, Z.,Liu, J.,Mao, H.,Liu, L.,Li, C.,Zhang, Y.,Li, P.,Ma, Y.,Sun, J.,Du, Q.,Li, J.,Wang, J.,Li, D.F.,Wu, B.,Shao, F.,Chen, Y.
The beta-d-manno-heptoses are immune agonists across kingdoms.
Science, 385:678-684, 2024

PubMed 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.

PubMed: 39116220
DOI: 10.1126/science.adk7314

Experimental method

X-RAY DIFFRACTION (2.3 Å)