Back to Search Start Over

Recognition and deubiquitination of free 40S for translational reset by Otu2

Authors :
Jingdong Cheng
Otto Berninghausen
Thomas Becker
Robert Buschauer
Yoshitaka Matsuo
Roland Beckmann
Nives Ivic
Toshifumi Inada
Thomas Froehlich
Ken Ikeuchi
Publication Year :
2021
Publisher :
Cold Spring Harbor Laboratory, 2021.

Abstract

In actively translating 80S ribosomes the ribosomal protein eS7 of the 40S subunit is monoubiquitinated by the E3 ligase Not41,2 and deubiquitinated by the deubiquitination enzyme Otu2 upon ribosomal subunit recycling3. Despite its importance for general efficiency of translation the exact role and structural basis for this specific translational reset are only poorly understood. Here we present biochemical and structural data showing that Otu2 can engage the recycled 40S subunit together with the recycling factors ABCE1 and Tma64 immediately after 60S dissociation for mRNA recycling, and that it dissociates before 48S initiation complex formation. A combined structural analysis of Otu2 and Otu2-40S complexes by X-ray crystallography, AlphaFold2 prediction4 and cryo-EM revealed how Otu2 can specifically be recruited to the 40S, but not to the 80S ribosome, for removal of the eS7-bound ubiquitin moiety. Here, interactions of the largely helical N-terminal domain of Otu2 to sites that are masked and therefore inaccessible in the 80S ribosome are of crucial importance. Collectively, we provide the structural basis for the Otu2 driven deubiquitination step providing a first mechanistic understanding of this translational reset step during ribosome recycling/(re)initiation.

Details

Database :
OpenAIRE
Accession number :
edsair.doi...........9e7aff32b294bfd843fd0e774bcdb1a3
Full Text :
https://doi.org/10.1101/2021.11.17.468975