4J8S

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

Summary for 4J8S

• Entry DOI: 10.2210/pdb4j8s/pdb
• Descriptor: CCR4-NOT transcription complex subunit 1, Tristetraprolin (3 entities in total)
• Functional Keywords: mif4g, protein-protein interaction, ttp, cytosol, protein binding
• Biological source: Homo sapiens (human); More
• Cellular location: Cytoplasm, P-body : A5YKK6; Nucleus : P26651
• Total number of polymer chains: 2
• Total formula weight: 25791.35

Authors

Frank, F.,Fabian, M.R.,Rouya, C.,Siddiqui, N.,Lai, W.S.,Karetnikov, A.,Blackshear, P.J.,Sonenberg, N.,Nagar, B. (deposition date: 2013-02-14, release date: 2013-05-08, Last modification date: 2024-02-28)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.55 Å)