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PDBsum entry 6npy
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Immune system
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PDB id
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6npy
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References listed in PDB file
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Key reference
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Title
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Structural mechanism for nek7-Licensed activation of nlrp3 inflammasome.
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Authors
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H.Sharif,
L.Wang,
W.L.Wang,
V.G.Magupalli,
L.Andreeva,
Q.Qiao,
A.V.Hauenstein,
Z.Wu,
G.Núñez,
Y.Mao,
H.Wu.
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Ref.
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Nature, 2019,
570,
338-343.
[DOI no: ]
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PubMed id
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Abstract
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The NLRP3 inflammasome can be activated by stimuli that include nigericin, uric
acid crystals, amyloid-β fibrils and extracellular ATP. The mitotic kinase NEK7
licenses the assembly and activation of the NLRP3 inflammasome in interphase.
Here we report a cryo-electron microscopy structure of inactive human NLRP3 in
complex with NEK7, at a resolution of 3.8 Å. The earring-shaped NLRP3 consists
of curved leucine-rich-repeat and globular NACHT domains, and the C-terminal
lobe of NEK7 nestles against both NLRP3 domains. Structural recognition between
NLRP3 and NEK7 is confirmed by mutagenesis both in vitro and in cells. Modelling
of an active NLRP3-NEK7 conformation based on the NLRC4 inflammasome predicts an
additional contact between an NLRP3-bound NEK7 and a neighbouring NLRP3.
Mutations to this interface abolish the ability of NEK7 or NLRP3 to rescue NLRP3
activation in NEK7-knockout or NLRP3-knockout cells. These data suggest that
NEK7 bridges adjacent NLRP3 subunits with bipartite interactions to mediate the
activation of the NLRP3 inflammasome.
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