PDBsum entry 4j8s

Protein binding

PDB id: 4j8s

Contents

Protein chains

180 a.a.

12 a.a.

Waters ×237

PDB id:

4j8s

Name:

Protein binding

Title:

Crystal structure of human cnot1 mif4g domain in complex with a ttp peptide

Structure:

Ccr4-not transcription complex subunit 1. Chain: a. Fragment: unp residues 800-1004. Synonym: ccr4-associated factor 1, negative regulator of transcription subunit 1 homolog, not1h, hnot1. Engineered: yes. Tristetraprolin. Chain: b. Fragment: unp residues 312-326.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: ad-005, cdc39, cnot1, kiaa1007, not1. Expressed in: escherichia coli. Expression_system_taxid: 469008. Synthetic: yes. Organism_taxid: 9606

Resolution:

1.55Å R-factor: 0.168 R-free: 0.188

Authors:

F.Frank,M.R.Fabian,C.Rouya,N.Siddiqui,W.S.Lai,A.Karetnikov, P.J.Blackshear,N.Sonenberg,B.Nagar

Key ref:

M.R.Fabian et al. (2013). Structural basis for the recruitment of the human CCR4-NOT deadenylase complex by tristetraprolin. Nat Struct Biol, 20, 735-739. PubMed id: 23644599 DOI: 10.1038/nsmb.2572

Date:

14-Feb-13 Release date: 08-May-13

Protein chain

A5YKK6  (CNOT1_HUMAN) -  CCR4-NOT transcription complex subunit 1 from Homo sapiens

Seq: 2376 a.a.

Struc: 180 a.a.*

Protein chain

P26651  (TTP_HUMAN) -  mRNA decay activator protein ZFP36 from Homo sapiens

Seq: 326 a.a.

Struc: 12 a.a.

* PDB and UniProt seqs differ at 3 residue positions (black crosses)

Enzyme reactions

• Enzyme class: Chains A, B: E.C.?

DOI no: 10.1038/nsmb.2572

Nat Struct Biol 20:735-739 (2013)

PubMed id: 23644599

Structural basis for the recruitment of the human CCR4-NOT deadenylase complex by tristetraprolin.

M.R.Fabian, F.Frank, C.Rouya, N.Siddiqui, W.S.Lai, A.Karetnikov, P.J.Blackshear, B.Nagar, N.Sonenberg.

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.