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PMID: 24121232 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Structure and assembly of the NOT module of the human CCR4-NOT complex.

Nature structural & molecular biology ·Vol. 20 ·No. 11 ·2013-11-00 ·Pages 1289-97

Boland A, Chen Y, Raisch T, Jonas S, Kuzuoğlu-Öztürk D, Wohlbold L, Weichenrieder O, Izaurralde E

Abstract

The 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.

MeSH Terms
Crystallography, X-Ray DNA Mutational Analysis Humans Models, Biological Models, Molecular Protein Binding Protein Conformation Protein Multimerization RNA, Messenger/metabolism Receptors, CCR4/metabolism Repressor Proteins/chemistry,genetics,metabolism Transcription Factors/chemistry,genetics,metabolism
Chemicals
CCR4 protein, human CNOT1 protein, human CNOT2 protein, human CNOT3 protein, human RNA, Messenger Receptors, CCR4 Repressor Proteins Transcription Factors
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Boland Andreas
1] Department of Biochemistry, Max Planck Institute for Developmental Biology, Tübingen, Germany. [2].
Chen Ying
Raisch Tobias
Jonas Stefanie
Kuzuoğlu-Öztürk Duygu
Wohlbold Lara
Weichenrieder Oliver
Izaurralde Elisa
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Article Info
Journal
Nature structural & molecular biology
Abbr.
Nat Struct Mol Biol
ISSN
1545-9985
DOI
10.1038/nsmb.2681
Published
2013-11-00
Epub
2013-00-13
Pages
1289-97
Language
English
Region
United States
NLM ID
101186374
Subset
IM
Databases
PDB
4C0D, 4C0E, 4C0F, 4C0G
External Links
PubMed source DOI: 10.1038/nsmb.2681 View journal details
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