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Visualizing the modification landscape of the human 60S ribosomal subunit at close to atomic resolution

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Item Type:Article
Title:Visualizing the modification landscape of the human 60S ribosomal subunit at close to atomic resolution
Creators Name:Wiechert, F., Unbehaun, A., Sprink, T., Seibel, H., Bürger, J., Loerke, J., Mielke, T., Diebolder, C.A., Schacherl, M. and Spahn, C.M.T.
Abstract:Chemical modifications of ribosomal RNAs (rRNAs) and proteins expand their topological repertoire, and together with the plethora of bound ligands, fine-tune ribosomal function. Detailed knowledge of this natural composition provides important insights into ribosome genesis and function and clarifies some aspects of ribosomopathies. The discovery of new structural properties and functional aspects of ribosomes has gone hand in hand with cryo-electron microscopy (cryo-EM) and its technological development. In line with the ability to visualize atomic details – a prerequisite for identifying chemical modifications and ligands in cryo-EM maps – in this work we present the structure of the 60S ribosomal subunit from HeLa cells at the very high global resolution of 1.78 Å. We identified 113 rRNA modifications and four protein modifications including uL2-His(β-ox)216, which stabilizes the local structure near the peptidyl transferase centre via an extended hydrogen-bonding network. We can differentiate metal ions Mg(2+) and K(+), polyamines spermine, spermidine and putrescine and identify thousands of water molecules binding to the 60S subunit. Approaching atomic resolution cryo-EM has become a powerful tool to examine fine details of macromolecular structures that will expand our knowledge about translation and other biological processes in the future and assess the variability of the chemical space due to differences between species/tissues or varying physicochemical environment.
Source:Nucleic Acids Research
ISSN:0305-1048
Publisher:Oxford University Press
Page Range:gkae1191
Date:10 December 2024
Official Publication:https://doi.org/10.1093/nar/gkae1191
PubMed:View item in PubMed

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