catalytic activity, acting on a tRNA / Cdc48p-Npl4p-Vms1p AAA ATPase complex / mitochondria-associated ubiquitin-dependent protein catabolic process / nuclear protein quality control by the ubiquitin-proteasome system / maturation of 5.8S rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / aminoacyl-tRNA hydrolase activity / pre-mRNA 5'-splice site binding / cleavage in ITS2 between 5.8S rRNA and LSU-rRNA of tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / response to cycloheximide / protein quality control for misfolded or incompletely synthesized proteins ...catalytic activity, acting on a tRNA / Cdc48p-Npl4p-Vms1p AAA ATPase complex / mitochondria-associated ubiquitin-dependent protein catabolic process / nuclear protein quality control by the ubiquitin-proteasome system / maturation of 5.8S rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / aminoacyl-tRNA hydrolase activity / pre-mRNA 5'-splice site binding / cleavage in ITS2 between 5.8S rRNA and LSU-rRNA of tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / response to cycloheximide / protein quality control for misfolded or incompletely synthesized proteins / maturation of 5.8S rRNA / SRP-dependent cotranslational protein targeting to membrane / GTP hydrolysis and joining of the 60S ribosomal subunit / ribosomal large subunit binding / Formation of a pool of free 40S subunits / Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC) / Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC) / negative regulation of mRNA splicing, via spliceosome / L13a-mediated translational silencing of Ceruloplasmin expression / preribosome, large subunit precursor / translational elongation / ribosomal large subunit export from nucleus / 90S preribosome / protein-RNA complex assembly / regulation of translational fidelity / ribosomal subunit export from nucleus / ERAD pathway / translational termination / RNA endonuclease activity / translation initiation factor activity / maturation of LSU-rRNA / rescue of stalled ribosome / maturation of LSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / assembly of large subunit precursor of preribosome / cytosolic ribosome assembly / ribosomal large subunit biogenesis / translational initiation / macroautophagy / maintenance of translational fidelity / modification-dependent protein catabolic process / rRNA processing / protein tag activity / ribosome biogenesis / 5S rRNA binding / large ribosomal subunit rRNA binding / cytosolic large ribosomal subunit / cytoplasmic translation / 加水分解酵素; エステル加水分解酵素 / rRNA binding / negative regulation of translation / ribosome / protein ubiquitination / structural constituent of ribosome / translation / response to antibiotic / mRNA binding / ubiquitin protein ligase binding / endoplasmic reticulum membrane / nucleolus / mitochondrion / RNA binding / nucleus / metal ion binding / cytosol / cytoplasm 類似検索 - 分子機能
VLRF1/Vms1 / : / Bacteroidetes VLRF1 release factor / 60s Acidic ribosomal protein / 60S acidic ribosomal protein P0 / Translation initiation factor IF6 / eIF-6 family / translation initiation factor 6 / : / : ...VLRF1/Vms1 / : / Bacteroidetes VLRF1 release factor / 60s Acidic ribosomal protein / 60S acidic ribosomal protein P0 / Translation initiation factor IF6 / eIF-6 family / translation initiation factor 6 / : / : / 50S ribosomal protein L10, insertion domain superfamily / 60S ribosomal protein L10P, insertion domain / Insertion domain in 60S ribosomal protein L10P / Ribosomal protein L29e / Ribosomal L29e protein family / Ribosomal protein L1, conserved site / Ribosomal protein L13e, conserved site / Ribosomal protein L13e signature. / Ribosomal protein L1 signature. / Ribosomal protein L1 / Ribosomal protein L22e / Ribosomal protein L22e superfamily / Ribosomal L22e protein family / Ribosomal protein L38e / Ribosomal protein L38e superfamily / Ribosomal L38e protein family / : / Ribosomal protein L27e, conserved site / Ribosomal protein L27e signature. / Ribosomal protein L44e signature. / Ribosomal protein L10e, conserved site / Ribosomal protein L10e signature. / Ribosomal protein L10e / Ribosomal protein L13e / Ribosomal protein L13e / Ribosomal protein L19, eukaryotic / 60S ribosomal protein L18a/ L20, eukaryotes / : / Ribosomal protein L24e, conserved site / Ribosomal protein L24e signature. / Ribosomal protein L44e / Ribosomal protein L19/L19e conserved site / Ribosomal protein L44 / Ribosomal protein L19e signature. / Ribosomal protein L34e, conserved site / Ribosomal protein L34e signature. / Ribosomal protein L5 eukaryotic, C-terminal / Ribosomal L18 C-terminal region / Ribosomal protein L6e signature. / 50S ribosomal protein L18Ae/60S ribosomal protein L20 and L18a / Ribosomal L40e family / Ribosomal protein L30e signature 1. / Ribosomal protein 50S-L18Ae/60S-L20/60S-L18A / Ribosomal proteins 50S-L18Ae/60S-L20/60S-L18A / Ribosomal_L40e / Ribosomal protein L40e / Ribosomal protein L40e superfamily / Ribosomal protein L1, 3-layer alpha/beta-sandwich / Ribosomal protein L30e signature 2. / Eukaryotic Ribosomal Protein L27, KOW domain / Ribosomal protein L23/L25, N-terminal / Ribosomal protein L30e, conserved site / Ribosomal protein L23, N-terminal domain / Ribosomal protein 60S L18 and 50S L18e / Ribosomal protein L27e / Ribosomal protein L27e superfamily / Ribosomal L27e protein family / Ribosomal protein L36e signature. / Ribosomal protein L39e, conserved site / Ribosomal protein L39e signature. / Ribosomal protein L18/L18-A/B/e, conserved site / Ribosomal protein L18e signature. / Ribosomal protein L34Ae / Ribosomal protein L34e / 60S ribosomal protein L19 / Ribosomal protein L35Ae, conserved site / Ribosomal protein L35Ae signature. / Ribosomal protein L30/YlxQ / 60S ribosomal protein L35 / Ribosomal Protein L6, KOW domain / Ribosomal protein L7A/L8 / Ribosomal protein L13, eukaryotic/archaeal / Ribosomal protein L6e / Ribosomal protein L18e / 60S ribosomal protein L6E / Ribosomal protein L37ae / Ribosomal L37ae protein family / 60S ribosomal protein L4, C-terminal domain / 60S ribosomal protein L4 C-terminal domain / Ribosomal protein L7, eukaryotic / Ribosomal protein L31e, conserved site / Ribosomal protein L31e signature. / Ribosomal_L19e / Ribosomal protein L30, N-terminal / Ribosomal L30 N-terminal domain / Ribosomal protein L19/L19e / Ribosomal protein L19/L19e, domain 1 / Ribosomal protein L19/L19e superfamily / Ribosomal protein L19e / Ribosomal protein L36e 類似検索 - ドメイン・相同性
Large ribosomal subunit protein uL15 / Large ribosomal subunit protein eL24A / Large ribosomal subunit protein uL23 / Large ribosomal subunit protein eL39 / Large ribosomal subunit protein uL10 / Large ribosomal subunit protein uL30A / Large ribosomal subunit protein uL6A / Large ribosomal subunit protein uL22A / Large ribosomal subunit protein uL24A / Large ribosomal subunit protein eL33A ...Large ribosomal subunit protein uL15 / Large ribosomal subunit protein eL24A / Large ribosomal subunit protein uL23 / Large ribosomal subunit protein eL39 / Large ribosomal subunit protein uL10 / Large ribosomal subunit protein uL30A / Large ribosomal subunit protein uL6A / Large ribosomal subunit protein uL22A / Large ribosomal subunit protein uL24A / Large ribosomal subunit protein eL33A / Large ribosomal subunit protein eL36A / Large ribosomal subunit protein eL29 / Large ribosomal subunit protein eL15A / Large ribosomal subunit protein eL22A / Large ribosomal subunit protein eL27A / Large ribosomal subunit protein eL31A / Ubiquitin-ribosomal protein eL40A fusion protein / Large ribosomal subunit protein eL20A / Large ribosomal subunit protein eL43A / Large ribosomal subunit protein eL42A / Large ribosomal subunit protein uL14A / Large ribosomal subunit protein uL1A / Large ribosomal subunit protein uL2A / Large ribosomal subunit protein eL18A / Large ribosomal subunit protein uL11A / Large ribosomal subunit protein eL19A / Large ribosomal subunit protein uL29A / Large ribosomal subunit protein uL4A / Large ribosomal subunit protein eL30 / Large ribosomal subunit protein uL3 / Large ribosomal subunit protein eL8A / Large ribosomal subunit protein uL18 / Large ribosomal subunit protein uL13A / Large ribosomal subunit protein eL14A / Large ribosomal subunit protein eL32 / Large ribosomal subunit protein uL16 / Large ribosomal subunit protein eL37A / Large ribosomal subunit protein eL38 / Large ribosomal subunit protein eL34A / Large ribosomal subunit protein eL6A / Large ribosomal subunit protein eL21A / tRNA endonuclease VMS1 / Eukaryotic translation initiation factor 6 / Large ribosomal subunit protein eL13A / Large ribosomal subunit protein uL5B 類似検索 - 構成要素
the Graduate School of Quantitative Biosciences Munich (QBM)
ドイツ
German Research Foundation
GRK1721
ドイツ
引用
ジャーナル: Nature / 年: 2019 タイトル: Structure and function of Vms1 and Arb1 in RQC and mitochondrial proteome homeostasis. 著者: Ting Su / Toshiaki Izawa / Matthias Thoms / Yui Yamashita / Jingdong Cheng / Otto Berninghausen / F Ulrich Hartl / Toshifumi Inada / Walter Neupert / Roland Beckmann / 要旨: Ribosome-associated quality control (RQC) provides a rescue pathway for eukaryotic cells to process faulty proteins after translational stalling of cytoplasmic ribosomes. After dissociation of ...Ribosome-associated quality control (RQC) provides a rescue pathway for eukaryotic cells to process faulty proteins after translational stalling of cytoplasmic ribosomes. After dissociation of ribosomes, the stalled tRNA-bound peptide remains associated with the 60S subunit and extended by Rqc2 by addition of C-terminal alanyl and threonyl residues (CAT tails), whereas Vms1 catalyses cleavage and release of the peptidyl-tRNA before or after addition of CAT tails. In doing so, Vms1 counteracts CAT-tailing of nuclear-encoded mitochondrial proteins that otherwise drive aggregation and compromise mitochondrial and cellular homeostasis. Here we present structural and functional insights into the interaction of Saccharomyces cerevisiae Vms1 with 60S subunits in pre- and post-peptidyl-tRNA cleavage states. Vms1 binds to 60S subunits with its Vms1-like release factor 1 (VLRF1), zinc finger and ankyrin domains. VLRF1 overlaps with the Rqc2 A-tRNA position and interacts with the ribosomal A-site, projecting its catalytic GSQ motif towards the CCA end of the tRNA, its Y285 residue dislodging the tRNA A73 for nucleolytic cleavage. Moreover, in the pre-state, we found the ABCF-type ATPase Arb1 in the ribosomal E-site, which stabilizes the delocalized A73 of the peptidyl-tRNA and stimulates Vms1-dependent tRNA cleavage. Our structural analysis provides mechanistic insights into the interplay of the RQC factors Vms1, Rqc2 and Arb1 and their role in the protection of mitochondria from the aggregation of toxic proteins.