Nature Alpha-kinase 1 is a cytosolic innate immune receptor for bacterial ADP- heptose https://www.nature.com/articles/s41586-018-0433-3 Abstract Immune recognition of pathogen-associated molecular patterns (PAMPs) by pattern recognition receptors often activates proinflammatory NF-κB signalling1. Recent studies indicate that the bacterial metabolite D-glycero -β-D-manno-heptose 1,7-bisphosphate (HBP) can activate NF-κB signalling in host cytosol2,3,4, but it is unclear whether HBP is a genuine PAMP and the cognate pattern recognition receptor has not been identified. Here we combined a transposon screen in Yersinia pseudotuberculosis with biochemical analyses and identified ADP-β-D-manno-heptose (ADP-Hep), which mediates type III secretion system-dependent NF-κB activation and cytokine expression. ADP-Hep, but not other heptose metabolites, could enter host cytosol to activate NF-κB. A CRISPR–Cas9 screen showed that activation of NF-κB by ADP-Hep involves an ALPK1 (alpha-kinase 1)–TIFA (TRAF-interacting protein with forkhead-associated domain) axis. ADP-Hep directly binds the N -terminal domain of ALPK1, stimulating its kinase domain to phosphorylate and activate TIFA. The crystal structure of the N-terminal domain of ALPK1 and ADP-Hep in complex revealed the atomic mechanism of this ligand– receptor recognition process. HBP was transformed by host adenylyltransferases into ADP-heptose 7-P, which could activate ALPK1 to a lesser extent than ADP-Hep. ADP-Hep (but not HBP) alone or during bacterial infection induced Alpk1-dependent inflammation in mice. Our findings identify ALPK1 and ADP-Hep as a pattern recognition receptor and an effective immunomodulator, respectively.
b*k
4 楼
主动和被动的区别。 银行绑定帐号的最stable
P*t
5 楼
LOL! Cute boy.
A*y
6 楼
X-ray structure...Nature...your point (tons of paper like these since the 80s)? Unfortunately, most biological system is not that simple but good enough for Nature.
【在 A******y 的大作中提到】 : X-ray structure...Nature...your point (tons of paper like these since the : 80s)? Unfortunately, most biological system is not that simple but good : enough for Nature.
【在 b*******0 的大作中提到】 : Nature : Alpha-kinase 1 is a cytosolic innate immune receptor for bacterial ADP- : heptose : https://www.nature.com/articles/s41586-018-0433-3 : Abstract : Immune recognition of pathogen-associated molecular patterns (PAMPs) by : pattern recognition receptors often activates proinflammatory NF-κB : signalling1. Recent studies indicate that the bacterial metabolite D-glycero : -β-D-manno-heptose 1,7-bisphosphate (HBP) can activate NF-κB signalling in : host cytosol2,3,4, but it is unclear whether HBP is a genuine PAMP and the
【在 A******y 的大作中提到】 : X-ray structure...Nature...your point (tons of paper like these since the : 80s)? Unfortunately, most biological system is not that simple but good : enough for Nature.