4J8S

Crystal structure of human CNOT1 MIF4G domain in complex with a TTP peptide

4J8S の概要

• エントリーDOI: 10.2210/pdb4j8s/pdb
• 分子名称: CCR4-NOT transcription complex subunit 1, Tristetraprolin (3 entities in total)
• 機能のキーワード: mif4g, protein-protein interaction, ttp, cytosol, protein binding
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Cytoplasm, P-body : A5YKK6; Nucleus : P26651
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 25791.35

構造登録者

Frank, F.,Fabian, M.R.,Rouya, C.,Siddiqui, N.,Lai, W.S.,Karetnikov, A.,Blackshear, P.J.,Sonenberg, N.,Nagar, B. (登録日: 2013-02-14, 公開日: 2013-05-08, 最終更新日: 2024-02-28)

主引用文献

Fabian, M.R.,Frank, F.,Rouya, C.,Siddiqui, N.,Lai, W.S.,Karetnikov, A.,Blackshear, P.J.,Nagar, B.,Sonenberg, N.
Structural basis for the recruitment of the human CCR4-NOT deadenylase complex by tristetraprolin.
Nat.Struct.Mol.Biol., 20:735-739, 2013

PubMed Abstract: 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.

PubMed: 23644599
DOI: 10.1038/nsmb.2572

実験手法

X-RAY DIFFRACTION (1.55 Å)