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-Structure paper
タイトル | Molecular basis of eIF5A-dependent CAT tailing in eukaryotic ribosome-associated quality control. |
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ジャーナル・号・ページ | Mol Cell, Vol. 83, Issue 4, Page 607-621.e4, Year 2023 |
掲載日 | 2023年2月16日 |
著者 | Petr Tesina / Shuhei Ebine / Robert Buschauer / Matthias Thoms / Yoshitaka Matsuo / Toshifumi Inada / Roland Beckmann / |
PubMed 要旨 | Ribosome-associated quality control (RQC) is a conserved process degrading potentially toxic truncated nascent peptides whose malfunction underlies neurodegeneration and proteostasis decline in aging. ...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. |
リンク | Mol Cell / PubMed:36804914 |
手法 | EM (単粒子) |
解像度 | 2.4 - 2.9 Å |
構造データ | EMDB-15296, PDB-8aaf: EMDB-15423, PDB-8agt: EMDB-15424, PDB-8agu: EMDB-15425, PDB-8agv: EMDB-15426, PDB-8agw: EMDB-15427, PDB-8agx: EMDB-15428, PDB-8agz: EMDB-15430: Yeast RQC complex in state A (pre-initiation) EMDB-15431: Yeast RQC complex in state B (A-site tRNA only) EMDB-15432: Yeast RQC complex in state C EMDB-15433: Yeast RQC complex in state I (translocation with A-site and E-site tRNAs) EMDB-15434: Yeast RQC complex in state J |
化合物 | ChemComp-MG: ChemComp-ZN: ChemComp-SPD: |
由来 |
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キーワード | TRANSLATION / ribosome-associated quality control / NEMF / Listerin / CAT tailing |