8ZDC

Cryo-EM structure of the human ubiquitylated pre-40S ribosome with RIOK3

Summary for 8ZDC

• Entry DOI: 10.2210/pdb8zdc/pdb
• EMDB information: 39957
• Descriptor: 18S rRNA, Small ribosomal subunit protein uS4, Small ribosomal subunit protein uS17, ... (38 entities in total)
• Functional Keywords: ubiquitylation, ribosome, riok3
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 38
• Total formula weight: 1483653.04

Authors

Huang, Z.,Wang, M.,Li, Y.,Beckmann, R.,Cheng, J. (deposition date: 2024-05-01, release date: 2025-02-12, Last modification date: 2025-03-12)

Primary citation

Huang, Z.,Diehl, F.F.,Wang, M.,Li, Y.,Song, A.,Chen, F.X.,Rosa-Mercado, N.A.,Beckmann, R.,Green, R.,Cheng, J.
RIOK3 mediates the degradation of 40S ribosomes.
Mol.Cell, 85:802-, 2025

PubMed Abstract: Cells tightly regulate ribosome homeostasis to adapt to changing environments. Ribosomes are degraded during stress, but the mechanisms responsible remain unclear. Here, we show that starvation induces the selective depletion of 40S ribosomes following their ubiquitylation by the E3 ligase RNF10. The atypical kinase RIOK3 specifically recognizes these ubiquitylated 40S ribosomes through a unique ubiquitin-interacting motif, visualized by cryoelectron microscopy (cryo-EM). RIOK3 binding and ubiquitin recognition are essential for 40S ribosome degradation during starvation. RIOK3 induces the degradation of ubiquitylated 40S ribosomes through progressive decay of their 18S rRNA beginning at the 3' end, as revealed by cryo-EM structures of degradation intermediates. Together, these data define a pathway and mechanism for stress-induced degradation of 40S ribosomes, directly connecting ubiquitylation to regulation of ribosome homeostasis.

PubMed: 39947183
DOI: 10.1016/j.molcel.2025.01.013

Experimental method

ELECTRON MICROSCOPY (3.8 Å)