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PDBsum entry 4j8s
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Protein binding
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PDB id
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4j8s
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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 basis for the recruitment of the human ccr4-Not deadenylase complex by tristetraprolin.
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Authors
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M.R.Fabian,
F.Frank,
C.Rouya,
N.Siddiqui,
W.S.Lai,
A.Karetnikov,
P.J.Blackshear,
B.Nagar,
N.Sonenberg.
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Ref.
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Nat Struct Biol, 2013,
20,
735-739.
[DOI no: ]
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PubMed id
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Abstract
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Tristetraprolin (TTP) is an RNA-binding protein that controls the inflammatory
response by limiting the expression of several proinflammatory cytokines. TTP
post-transcriptionally represses gene expression by interacting with AU-rich
elements (AREs) in 3' untranslated regions of target mRNAs and subsequently
engenders their deadenylation and decay. TTP accomplishes these tasks, at least
in part, by recruiting the multisubunit CCR4-NOT deadenylase complex to the
mRNA. Here we identify an evolutionarily conserved C-terminal motif in human TTP
that directly binds a central domain of CNOT1, a core subunit of the CCR4-NOT
complex. A high-resolution crystal structure of the TTP-CNOT1 complex was
determined, providing the first structural insight, to our knowledge, into an
ARE-binding protein bound to the CCR4-NOT complex. Mutations at the CNOT1-TTP
interface impair TTP-mediated deadenylation, demonstrating the significance of
this interaction in TTP-mediated gene silencing.
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