4CT5

DDX6

Summary for 4CT5

• Entry DOI: 10.2210/pdb4ct5/pdb
• Related: 4CT4
• Descriptor: DDX6, ACETATE ION (2 entities in total)
• Functional Keywords: hydrolase
• Biological source: HOMO SAPIENS (HUMAN)
• Cellular location: Cytoplasm, P-body: P26196
• Total number of polymer chains: 2
• Total formula weight: 86496.48

Authors

Ozgur, S.,Basquin, J.,Conti, E. (deposition date: 2014-03-12, release date: 2014-05-07, Last modification date: 2023-12-20)

Primary citation

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, 54:751-, 2014

PubMed Abstract: 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.

PubMed: 24768538
DOI: 10.1016/J.MOLCEL.2014.03.036

Experimental method

X-RAY DIFFRACTION (3 Å)