Abstract

NOT1, NOT10, and NOT11 form a conserved module in the CCR4-NOT complex, critical for post-transcriptional regulation in eukaryotes, but how this module contributes to the functions of the CCR4-NOT remains poorly understood. Here, we present cryo-EM structures of human and chicken NOT1:NOT10:NOT11 ternary complexes to sub-3 Å resolution, revealing an evolutionarily conserved, flexible structure. Through biochemical dissection studies, which include the Drosophila orthologs, we show that the module assembly is hierarchical, with NOT11 binding to NOT10, which then organizes it for binding to NOT1. A short proline-rich motif in NOT11 stabilizes the entire module assembly.

Structural and biochemical characterization of the human, chicken, and Drosophila NOT1:NOT10:NOT11 ternary complexes reveal the evolutionarily conserved NOT10:11 module, hierarchical assembly of the complex.

Details

Title
Structure and assembly of the NOT10:11 module of the CCR4-NOT complex
Author
Levdansky, Yevgen 1   VIAFID ORCID Logo  ; Raisch, Tobias 2   VIAFID ORCID Logo  ; Deme, Justin C. 3   VIAFID ORCID Logo  ; Pekovic, Filip 1   VIAFID ORCID Logo  ; Elmlund, Hans 3 ; Lea, Susan M. 3   VIAFID ORCID Logo  ; Valkov, Eugene 4   VIAFID ORCID Logo 

1  National Cancer Institute, RNA Biology Laboratory, Center for Cancer Research, Frederick, USA (GRID:grid.48336.3a) (ISNI:0000 0004 1936 8075) 
2  Max Planck Institute of Molecular Physiology, Department of Structural Biochemistry, Dortmund, Germany (GRID:grid.418441.c) (ISNI:0000 0004 0491 3333) 
3  National Cancer Institute, Center for Structural Biology, Center for Cancer Research, Frederick, USA (GRID:grid.48336.3a) (ISNI:0000 0004 1936 8075) 
4  National Cancer Institute, RNA Biology Laboratory, Center for Cancer Research, Frederick, USA (GRID:grid.48336.3a) (ISNI:0000 0004 1936 8075); National Cancer Institute, Center for Structural Biology, Center for Cancer Research, Frederick, USA (GRID:grid.48336.3a) (ISNI:0000 0004 1936 8075) 
Pages
739
Publication year
2023
Publication date
2023
Publisher
Nature Publishing Group
e-ISSN
23993642
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s42003-023-05122-4
ProQuest document ID
2838517885
Copyright
© This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2023. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.