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PDBsum entry 5ep4
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Transcription
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PDB id
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5ep4
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References listed in PDB file
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Key reference
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Title
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Structure, Regulation, And inhibition of the quorum-Sensing signal integrator luxo.
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Authors
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H.Boyaci,
T.Shah,
A.Hurley,
B.Kokona,
Z.Li,
C.Ventocilla,
P.D.Jeffrey,
M.F.Semmelhack,
R.Fairman,
B.L.Bassler,
F.M.Hughson.
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Ref.
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Plos Biol, 2016,
14,
e1002464.
[DOI no: ]
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PubMed id
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Abstract
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In a process called quorum sensing, bacteria communicate with chemical signal
molecules called autoinducers to control collective behaviors. In pathogenic
vibrios, including Vibrio cholerae, the accumulation of autoinducers triggers
repression of genes responsible for virulence factor production and biofilm
formation. The vibrio autoinducer molecules bind to transmembrane receptors of
the two-component histidine sensor kinase family. Autoinducer binding
inactivates the receptors' kinase activities, leading to dephosphorylation and
inhibition of the downstream response regulator LuxO. Here, we report the X-ray
structure of LuxO in its unphosphorylated, autoinhibited state. Our structure
reveals that LuxO, a bacterial enhancer-binding protein of the AAA+ ATPase
superfamily, is inhibited by an unprecedented mechanism in which a linker that
connects the catalytic and regulatory receiver domains occupies the ATPase
active site. The conformational change that accompanies receiver domain
phosphorylation likely disrupts this interaction, providing a mechanistic
rationale for LuxO activation. We also determined the crystal structure of the
LuxO catalytic domain bound to a broad-spectrum inhibitor. The inhibitor binds
in the ATPase active site and recapitulates elements of the natural regulatory
mechanism. Remarkably, a single inhibitor molecule may be capable of inhibiting
an entire LuxO oligomer.
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