4c0f
From Proteopedia
Structure of the NOT-box domain of human CNOT2
Structural highlights
FunctionCNOT2_HUMAN Component of the CCR4-NOT complex which is one of the major cellular mRNA deadenylases and is linked to various cellular processes including bulk mRNA degradation, miRNA-mediated repression, translational repression during translational initiation and general transcription regulation. Additional complex functions may be a consequence of its influence on mRNA expression. Required for the CCR4-NOT complex structural integrity. Can repress transcription and may link the CCR4-NOT complex to transcriptional regulation; the repressive function may specificly involve the N-Cor repressor complex containing HDAC3, NCOR1 and NCOR2. Involved in the maintenance of emryonic stem (ES) cell identity.[1] [2] [3] [4] Publication Abstract from PubMedThe CCR4-NOT deadenylase complex is a master regulator of translation and mRNA stability. Its NOT module orchestrates recruitment of the catalytic subunits to target mRNAs. We report the crystal structure of the human NOT module formed by the CNOT1, CNOT2 and CNOT3 C-terminal (-C) regions. CNOT1-C provides a rigid scaffold consisting of two perpendicular stacks of HEAT-like repeats. CNOT2-C and CNOT3-C heterodimerize through their SH3-like NOT-box domains. The heterodimer is stabilized and tightly anchored to the surface of CNOT1 through an unexpected intertwined arrangement of peptide regions lacking defined secondary structure. These assembly peptides mold onto their respective binding surfaces and form extensive interfaces. Mutagenesis of individual interfaces and perturbation of endogenous protein ratios cause defects in complex assembly and mRNA decay. Our studies provide a structural framework for understanding the recruitment of the CCR4-NOT complex to mRNA targets. Structure and assembly of the NOT module of the human CCR4-NOT complex.,Boland A, Chen Y, Raisch T, Jonas S, Kuzuoglu-Ozturk D, Wohlbold L, Weichenrieder O, Izaurralde E Nat Struct Mol Biol. 2013 Oct 13. doi: 10.1038/nsmb.2681. PMID:24121232[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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