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  Structural impact of K63 ubiquitin on yeast translocating ribosomes under oxidative stress

Zhou, Y., Kastritis, P. L., Dougherty, S. E., Bouvette, J., Hsu, A. L. L., Burbaum, L., et al. (2020). Structural impact of K63 ubiquitin on yeast translocating ribosomes under oxidative stress. Proceedings of the National Academy of Sciences of the United States of America, 117(36), 22157-22166. doi:10.1073/pnas.2005301117.

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 Creators:
Zhou, Ye, Author
Kastritis, P. L., Author
Dougherty, S. E., Author
Bouvette, J., Author
Hsu, A. L. L., Author
Burbaum, L.1, 2, Author           
Mosalaganti, S., Author
Pfeffer, S.2, Author           
Hagen, W. J. H., Author
Förster, Friedrich2, Author           
Borgnia, M. J., Author
Vogel, Christine, Author
Beck, MartinMartin, Author
Bartesaghi, A., Author
Silva, G. M., Author
Affiliations:
1Schwille, Petra / Cellular and Molecular Biophysics, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565169              
2Baumeister, Wolfgang / Molecular Structural Biology, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565142              

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Free keywords: K63 ubiquitin ribosome cryo-EM oxidative stress translation cryo-em in-situ translation stalk complexes toolbox binding Science & Technology - Other Topics
 Abstract: Subpopulations of ribosomes are responsible for fine tuning the control of protein synthesis in dynamic environments. K63 ubiquitination of ribosomes has emerged as a new posttranslational modification that regulates protein synthesis during cellular response to oxidative stress. K63 ubiquitin, a type of ubiquitin chain that functions independently of the proteasome, modifies several sites at the surface of the ribosome, however, we lack a molecular understanding on how this modification affects ribosome structure and function. Using cryoelectron microscopy (cryo-EM), we resolved the first three-dimensional (3D) structures of K63 ubiquitinated ribosomes from oxidatively stressed yeast cells at 3.5-3.2 angstrom resolution. We found that K63 ubiquitinated ribosomes are also present in a polysome arrangement, similar to that observed in yeast polysomes, which we determined using cryoelectron tomography (cryo-ET). We further showed that K63 ubiquitinated ribosomes are captured uniquely at the rotated pretranslocation stage of translation elongation. In contrast, cryo-EM structures of ribosomes from mutant cells lacking K63 ubiquitin resolved at 4.4-2.7 angstrom showed 805 ribosomes represented in multiple states of translation, suggesting that K63 ubiquitin regulates protein synthesis at a selective stage of elongation. Among the observed structural changes, ubiquitin mediates the destabilization of proteins in the 60S P-stalk and in the 40S beak, two binding regions of the eukaryotic elongation factor eEF2. These changes would impact eEF2 function, thus, inhibiting translocation. Our findings help uncover the molecular effects of K63 ubiquitination on ribosomes, providing a model of translation control during oxidative stress, which supports elongation halt at pretranslocation.

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Language(s): eng - English
 Dates: 2020-08-27
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Identifiers: Other: WOS:000572964500018
DOI: 10.1073/pnas.2005301117
ISSN: 0027-8424
 Degree: -

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Title: Proceedings of the National Academy of Sciences of the United States of America
  Other : PNAS
  Other : Proceedings of the National Academy of Sciences of the USA
  Abbreviation : Proc. Natl. Acad. Sci. U. S. A.
Source Genre: Journal
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Publ. Info: Washington, D.C. : National Academy of Sciences
Pages: - Volume / Issue: 117 (36) Sequence Number: - Start / End Page: 22157 - 22166 Identifier: ISSN: 0027-8424
CoNE: https://pure.mpg.de/cone/journals/resource/954925427230