| Structural highlights
4ct4 is a 4 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | ,
| | Related: | 4ct5, 4ct6, 4ct7 |
| Resources: | FirstGlance, OCA, RCSB, PDBsum |
Disease
[DDX6_HUMAN] Note=A chromosomal aberration involving DDX6 may be a cause of hematopoietic tumors such as B-cell lymphomas. Translocation t(11;14)(q23;q32).
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] [DDX6_HUMAN] In the process of mRNA degradation, may play a role in mRNA decapping.
Publication Abstract from PubMed
MicroRNAs (miRNAs) control gene expression by regulating mRNA translation and stability. The CCR4-NOT complex is a key effector of miRNA function acting downstream of GW182/TNRC6 proteins. We show that miRNA-mediated repression requires the central region of CNOT1, the scaffold protein of CCR4-NOT. A CNOT1 domain interacts with CNOT9, which in turn interacts with the silencing domain of TNRC6 in a tryptophan motif-dependent manner. These interactions are direct, as shown by the structure of a CNOT9-CNOT1 complex with bound tryptophan. Another domain of CNOT1 with an MIF4G fold recruits the DEAD-box ATPase DDX6, a known translational inhibitor. Structural and biochemical approaches revealed that CNOT1 modulates the conformation of DDX6 and stimulates ATPase activity. Structure-based mutations showed that the CNOT1 MIF4G-DDX6 interaction is important for miRNA-mediated repression. These findings provide insights into the repressive steps downstream of the GW182/TNRC6 proteins and the role of the CCR4-NOT complex in posttranscriptional regulation in general.
Structural and Biochemical Insights to the Role of the CCR4-NOT Complex and DDX6 ATPase in MicroRNA Repression.,Mathys H, Basquin J, Ozgur S, Czarnocki-Cieciura M, Bonneau F, Aartse A, Dziembowski A, Nowotny M, Conti E, Filipowicz W Mol Cell. 2014 Apr 22. pii: S1097-2765(14)00269-X. doi:, 10.1016/j.molcel.2014.03.036. PMID:24768538[3]
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
- ↑ Mathys H, Basquin J, Ozgur S, Czarnocki-Cieciura M, Bonneau F, Aartse A, Dziembowski A, Nowotny M, Conti E, Filipowicz W. Structural and Biochemical Insights to the Role of the CCR4-NOT Complex and DDX6 ATPase in MicroRNA Repression. Mol Cell. 2014 Apr 22. pii: S1097-2765(14)00269-X. doi:, 10.1016/j.molcel.2014.03.036. PMID:24768538 doi:http://dx.doi.org/10.1016/j.molcel.2014.03.036
|
