6r84

Yeast Vms1 (Q295L)-60S ribosomal subunit complex (pre-state with Arb1)

spinqualitylabelsall models 6r84, resolution 3.60Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6r84 is a 50 chain structure with sequence from [1] and Saccharomyces cerevisiae. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: ZN NonStd Res: MSE, UNK Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [RL25_YEAST] This protein binds to a specific region on the 26S rRNA. [RL12A_YEAST] This protein binds directly to 26S ribosomal RNA.[HAMAP-Rule:MF_00736] [VMS1_YEAST] Involved in the endoplasmic reticulum (ER)-associated degradation (ERAD) pathway. Component of an evolutionarily conserved system for ubiquitin-mediated mitochondria-associated protein degradation (MAD), which is necessary to maintain mitochondrial, cellular, and organismal viability. [ARB1_YEAST] Stimulates 40S and 60S ribosome biogenesis. [RL40A_YEAST] Ubiquitin: Exists either covalently attached to another protein, or free (unanchored). When covalently bound, it is conjugated to target proteins via an isopeptide bond either as a monomer (monoubiquitin), a polymer linked via different Lys residues of the ubiquitin (polyubiquitin chains) or a linear polymer linked via the initiator Met of the ubiquitin (linear polyubiquitin chains). Polyubiquitin chains, when attached to a target protein, have different functions depending on the Lys residue of the ubiquitin that is linked: Lys-6-linked may be involved in DNA repair; Lys-11-linked is involved in ERAD (endoplasmic reticulum-associated degradation) and in cell-cycle regulation; Lys-29-linked is involved in lysosomal degradation; Lys-33-linked is involved in kinase modification; Lys-48-linked is involved in protein degradation via the proteasome; Lys-63-linked is involved in endocytosis, and DNA-damage responses. Linear polymer chains formed via attachment by the initiator Met lead to cell signaling. Ubiquitin is usually conjugated to Lys residues of target proteins, however, in rare cases, conjugation to Cys or Ser residues has been observed. When polyubiquitin is free (unanchored-polyubiquitin), it also has distinct roles, such as in activation of protein kinases, and in signaling (By similarity). 60S ribosomal protein L40-A: Component of the ribosome, a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell. The small ribosomal subunit (SSU) binds messenger RNAs (mRNAs) and translates the encoded message by selecting cognate aminoacyl-transfer RNA (tRNA) molecules. The large subunit (LSU) contains the ribosomal catalytic site termed the peptidyl transferase center (PTC), which catalyzes the formation of peptide bonds, thereby polymerizing the amino acids delivered by tRNAs into a polypeptide chain. The nascent polypeptides leave the ribosome through a tunnel in the LSU and interact with protein factors that function in enzymatic processing, targeting, and the membrane insertion of nascent chains at the exit of the ribosomal tunnel (PubMed:22096102). eL40 is essential for translation of a subset of cellular transcripts, including stress response transcripts, such as DDR2 (PubMed:23169626). [RL4A_YEAST] Participates in the regulation of the accumulation of its own mRNA. [RLA0_YEAST] Ribosomal protein P0 is the functional equivalent of E.coli protein L10. [RL37A_YEAST] Binds to the 23S rRNA (By similarity). [RL11B_YEAST] Binds to 5S ribosomal RNA. [RL5_YEAST] Binds 5S RNA and is required for 60S subunit assembly. [IF6_YEAST] Binds to the 60S ribosomal subunit and prevents its association with the 40S ribosomal subunit to form the 80S initiation complex in the cytoplasm. Is also involved in ribosome biogenesis. Associates with pre-60S subunits in the nucleus and is involved in its nuclear export. Cytoplasmic release of TIF6 from 60S subunits and nuclear relocalization is promoted by the GTPase RIA1/EFL1 and by SDO1. Also required for pre-rRNA processing. Publication Abstract from PubMed Ribosome-associated quality control (RQC) provides a rescue pathway for eukaryotic cells to process faulty proteins after translational stalling of cytoplasmic ribosomes(1-6). 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)(7-9), whereas Vms1 catalyses cleavage and release of the peptidyl-tRNA before or after addition of CAT tails(10-12). In doing so, Vms1 counteracts CAT-tailing of nuclear-encoded mitochondrial proteins that otherwise drive aggregation and compromise mitochondrial and cellular homeostasis(13). 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. Structure and function of Vms1 and Arb1 in RQC and mitochondrial proteome homeostasis.,Su T, Izawa T, Thoms M, Yamashita Y, Cheng J, Berninghausen O, Hartl FU, Inada T, Neupert W, Beckmann R Nature. 2019 Jun 12. pii: 10.1038/s41586-019-1307-z. doi:, 10.1038/s41586-019-1307-z. PMID:31189955 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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