EMD-15428

Single-particle
2.6 Å
EMD-15428 Deposition: 20/07/2022
Map released: 08/03/2023
Last modified: 09/10/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links

EMD-15428

Yeast RQC complex in state with the RING domain of Ltn1 in the OUT position

EMD-15428

Single-particle
2.6 Å
EMD-15428 Deposition: 20/07/2022
Map released: 08/03/2023
Last modified: 09/10/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Sample Organism: Saccharomyces cerevisiae
Sample: Yeast RQC complex in state with the RING domain of Ltn1 in the OUT position
Fitted models: 8agz (Avg. Q-score: 0.512)

Deposition Authors: Tesina P , Buschauer R, Beckmann R
Molecular basis of eIF5A-dependent CAT tailing in eukaryotic ribosome-associated quality control.
Tesina P , Ebine S, Buschauer R, Thoms M, Matsuo Y , Inada T, Beckmann R
(2023) Mol Cell , 83 , 607 - 621.e4
PUBMED: 36804914
DOI: doi:10.1016/j.molcel.2023.01.020
ISSN: 1097-2765
ASTM: MOCEFL
Abstract:
Ribosome-associated quality control (RQC) is a conserved process degrading potentially toxic truncated nascent peptides whose malfunction underlies neurodegeneration and proteostasis decline in aging. During RQC, dissociation of stalled ribosomes is followed by elongation of the nascent peptide with alanine and threonine residues, driven by Rqc2 independently of mRNA, the small ribosomal subunit and guanosine triphosphate (GTP)-hydrolyzing factors. The resulting CAT tails (carboxy-terminal tails) and ubiquitination by Ltn1 mark nascent peptides for proteasomal degradation. Here we present ten cryogenic electron microscopy (cryo-EM) structures, revealing the mechanistic basis of individual steps of the CAT tailing cycle covering initiation, decoding, peptidyl transfer, and tRNA translocation. We discovered eIF5A as a crucial eukaryotic RQC factor enabling peptidyl transfer. Moreover, we observed dynamic behavior of RQC factors and tRNAs allowing for processivity of the CAT tailing cycle without additional energy input. Together, these results elucidate key differences as well as common principles between CAT tailing and canonical translation.