4j8s

From Proteopedia

(Difference between revisions)

Revision as of 04:25, 25 December 2014

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

Structural highlights

4j8s is a 2 chain structure with sequence from [1] and Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Gene:	AD-005, CDC39, CNOT1, KIAA1007, NOT1 (Homo sapiens)
Resources:	FirstGlance, OCA, RCSB, PDBsum

Function

[CNOT1_HUMAN] Belongs to the CCR4-NOT complex that functions as general transcription regulation complex. Acts as a transcriptional repressor. Represses the ligand-dependent transcriptional activation by nuclear receptors.^[1] ^[2] [TTP_HUMAN] mRNA-binding protein involved in post-transcriptional regulation of AU-rich element (ARE)-containing mRNAs. Acts by specifically binding ARE-containing mRNAs and promoting their degradation. Plays a key role in the post-transcriptional regulation of tumor necrosis factor (TNF).^[3]

Publication Abstract from PubMed

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.

Structural basis for the recruitment of the human CCR4-NOT deadenylase complex by tristetraprolin.,Fabian MR, Frank F, Rouya C, Siddiqui N, Lai WS, Karetnikov A, Blackshear PJ, Nagar B, Sonenberg N Nat Struct Mol Biol. 2013 Jun;20(6):735-9. doi: 10.1038/nsmb.2572. Epub 2013 May , 5. PMID:23644599^[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Albert TK, Lemaire M, van Berkum NL, Gentz R, Collart MA, Timmers HT. Isolation and characterization of human orthologs of yeast CCR4-NOT complex subunits. Nucleic Acids Res. 2000 Feb 1;28(3):809-17. PMID:10637334
↑ Winkler GS, Mulder KW, Bardwell VJ, Kalkhoven E, Timmers HT. Human Ccr4-Not complex is a ligand-dependent repressor of nuclear receptor-mediated transcription. EMBO J. 2006 Jul 12;25(13):3089-99. Epub 2006 Jun 15. PMID:16778766 doi:7601194
↑ Stoecklin G, Stubbs T, Kedersha N, Wax S, Rigby WF, Blackwell TK, Anderson P. MK2-induced tristetraprolin:14-3-3 complexes prevent stress granule association and ARE-mRNA decay. EMBO J. 2004 Mar 24;23(6):1313-24. Epub 2004 Mar 11. PMID:15014438 doi:10.1038/sj.emboj.7600163
↑ Fabian MR, Frank F, Rouya C, Siddiqui N, Lai WS, Karetnikov A, Blackshear PJ, Nagar B, Sonenberg N. Structural basis for the recruitment of the human CCR4-NOT deadenylase complex by tristetraprolin. Nat Struct Mol Biol. 2013 Jun;20(6):735-9. doi: 10.1038/nsmb.2572. Epub 2013 May , 5. PMID:23644599 doi:10.1038/nsmb.2572

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4j8s"

@@ Line 6: / Line 6: @@
 <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4j8s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4j8s OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4j8s RCSB], [http://www.ebi.ac.uk/pdbsum/4j8s PDBsum]</span></td></tr>
 </table>
+== Function ==
+[[http://www.uniprot.org/uniprot/CNOT1_HUMAN CNOT1_HUMAN]] Belongs to the CCR4-NOT complex that functions as general transcription regulation complex. Acts as a transcriptional repressor. Represses the ligand-dependent transcriptional activation by nuclear receptors.<ref>PMID:10637334</ref> <ref>PMID:16778766</ref>  [[http://www.uniprot.org/uniprot/TTP_HUMAN TTP_HUMAN]] mRNA-binding protein involved in post-transcriptional regulation of AU-rich element (ARE)-containing mRNAs. Acts by specifically binding ARE-containing mRNAs and promoting their degradation. Plays a key role in the post-transcriptional regulation of tumor necrosis factor (TNF).<ref>PMID:15014438</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==

4j8s

From Proteopedia

Revision as of 04:25, 25 December 2014

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

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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