We apologize for Proteopedia being slow to respond. For the past two years, a new implementation of Proteopedia has been being built. Soon, it will replace this 18-year old system. All existing content will be moved to the new system at a date that will be announced here.

5anr

From Proteopedia

Jump to: navigation, search

Structure of a human 4E-T - DDX6 - CNOT1 complex

Structural highlights

5anr is a 3 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.102Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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]

Publication Abstract from PubMed

The DEAD-box protein DDX6 is a central component of translational repression mechanisms in maternal mRNA storage in oocytes and microRNA-mediated silencing in somatic cells. DDX6 interacts with the CCR4-NOT complex and functions in concert with several post-transcriptional regulators, including Edc3, Pat1, and 4E-T. We show that the conserved CUP-homology domain (CHD) of human 4E-T interacts directly with DDX6 in both the presence and absence of the central MIF4G domain of CNOT1. The 2.1-A resolution structure of the corresponding ternary complex reveals how 4E-T CHD wraps around the RecA2 domain of DDX6 and contacts CNOT1. Although 4E-T CHD lacks recognizable sequence similarity with Edc3 or Pat1, it shares the same DDX6-binding surface. In contrast to 4E-T, however, the Edc3 and Pat1 FDF motifs dissociate from DDX6 upon CNOT1 MIF4G binding in vitro. The results underscore the presence of a complex network of simultaneous and/or mutually exclusive interactions in DDX6-mediated repression.

Structure of a Human 4E-T/DDX6/CNOT1 Complex Reveals the Different Interplay of DDX6-Binding Proteins with the CCR4-NOT Complex.,Ozgur S, Basquin J, Kamenska A, Filipowicz W, Standart N, Conti E Cell Rep. 2015 Oct 27;13(4):703-11. doi: 10.1016/j.celrep.2015.09.033. Epub 2015 , Oct 17. PMID:26489469^[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
↑ Ozgur S, Basquin J, Kamenska A, Filipowicz W, Standart N, Conti E. Structure of a Human 4E-T/DDX6/CNOT1 Complex Reveals the Different Interplay of DDX6-Binding Proteins with the CCR4-NOT Complex. Cell Rep. 2015 Oct 27;13(4):703-11. doi: 10.1016/j.celrep.2015.09.033. Epub 2015 , Oct 17. PMID:26489469 doi:http://dx.doi.org/10.1016/j.celrep.2015.09.033