4CRU

Complex of human CNOT9 and CNOT1 including one tryptophan

Summary for 4CRU

• Entry DOI: 10.2210/pdb4cru/pdb
• Related: 2FV2 4CRV
• Descriptor: CCR4-NOT TRANSCRIPTION COMPLEX SUBUNIT 1, CELL DIFFERENTIATION PROTEIN RCD1 HOMOLOG, GLYCEROL, ... (4 entities in total)
• Functional Keywords: gene regulation, tnrc6 binding, mirisc, mrna silencing, mrna deadenylation, argonaute, transcription
• Biological source: HOMO SAPIENS (HUMAN); More
• Cellular location: Cytoplasm, P-body: A5YKK6; Nucleus (By similarity): Q92600
• Total number of polymer chains: 2
• Total formula weight: 60430.98

Authors

Chen, Y.,Boland, A.,Izaurralde, E.,Weichenrieder, O. (deposition date: 2014-03-01, release date: 2014-05-07, Last modification date: 2023-12-20)

Primary citation

Chen, Y.,Boland, A.,Kuzuoglu-Ozturk, D.,Bawankar, P.,Loh, B.,Chang, C.T.,Weichenrieder, O.,Izaurralde, E.
A Ddx6-Cnot1 Complex and W-Binding Pockets in Cnot9 Reveal Direct Links between Mirna Target Recognition and Silencing
Mol.Cell, 54:737-, 2014

PubMed Abstract: CCR4-NOT is a major effector complex in miRNA-mediated gene silencing. It is recruited to miRNA targets through interactions with tryptophan (W)-containing motifs in TNRC6/GW182 proteins and is required for both translational repression and degradation of miRNA targets. Here, we elucidate the structural basis for the repressive activity of CCR4-NOT and its interaction with TNRC6/GW182s. We show that the conserved CNOT9 subunit attaches to a domain of unknown function (DUF3819) in the CNOT1 scaffold. The resulting complex provides binding sites for TNRC6/GW182, and its crystal structure reveals tandem W-binding pockets located in CNOT9. We further show that the CNOT1 MIF4G domain interacts with the C-terminal RecA domain of DDX6, a translational repressor and decapping activator. The crystal structure of this complex demonstrates striking similarity to the eIF4G-eIF4A complex. Together, our data provide the missing physical links in a molecular pathway that connects miRNA target recognition with translational repression, deadenylation, and decapping.

PubMed: 24768540
DOI: 10.1016/J.MOLCEL.2014.03.034

Experimental method

X-RAY DIFFRACTION (1.65 Å)