6q8y | pdb_00006q8y

Cryo-EM structure of the mRNA translating and degrading yeast 80S ribosome-Xrn1 nuclease complex

spinqualitylabelsall models 6q8y, resolution 3.10Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6q8y is a 82 chain structure with sequence from Atcc 18824 and Saccharomyces cerevisiae. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: MG, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [XRN1_YEAST] Multifunctional protein that exhibits several independent functions at different levels of the cellular processes. 5'-3' exonuclease component of the nonsense-mediated mRNA decay (NMD) which is a highly conserved mRNA degradation pathway, an RNA surveillance system whose role is to identify and rid cells of mRNA with premature termination codons and thus prevents accumulation of potentially harmful truncated proteins. The NMD pathway has a second role regulating the decay of wild-type mRNAs, and especially mRNAs that are important for telomere functions. Participate in CTH2-mediated and VTS1-mediated mRNA turnover. Involved in the degradation of several hypomodified mature tRNA species and participates in the 5'-processing or the degradation of the snoRNA precursors and rRNA processing. Involved in defense against virus and suppresses viral RNA recombination by rapidly removing the 5'-truncated RNAs, the substrates of recombination, and thus reducing the chance for recombination to occur in the parental strain. Required for the assembly of the virus-like particles of the Ty3 retrotransposon and contributes to the efficient generation of narnavirus 20S RNA by playing a major role in the elimination of the non-viral upstream sequences from the primary transcripts. Degrades single-stranded DNA (ss-DNA) and can renature complementary ss-DNA as well as catalyzes the formation of heteroduplex DNA from circular ss-DNA and homologous linear ds-DNA in vitro. Acts as a microtubule-associated protein which interacts with cytoplasmic microtubules through beta-tubulin and promotes in vitro assembly of tubulin into microtubules. Associates with microtubule functions such as chromosome transmission, nuclear migration, and SPB duplication. Has also a role in G1 to S transition and is involved in nuclear fusion during karyogamy. Required for the expression of ROK1 at the post-transcriptional level and for the alpha-factor induction of the karyogamy genes KAR3 and KAR4. Plays a role in filamentous growth. [RSSA1_YEAST] Required for the assembly and/or stability of the 40S ribosomal subunit. Required for the processing of the 20S rRNA-precursor to mature 18S rRNA in a late step of the maturation of 40S ribosomal subunits. [RL37A_YEAST] Binds to the 23S rRNA (By similarity). [RS21A_YEAST] Required for the processing of the 20S rRNA-precursor to mature 18S rRNA in a late step of the maturation of 40S ribosomal subunits. Has a physiological role leading to 18S rRNA stability. [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). [RS15_YEAST] Involved in the nuclear export of the small ribosomal subunit. Has a role in the late stage of the assembly of pre-40S particles within the nucleus and controls their export to the cytoplasm. [RS27A_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). 40S ribosomal protein S31 is a component of the 40S subunit of the ribosome (By similarity). [RS9A_YEAST] Involved in nucleolar processing of pre-18S ribosomal RNA and ribosome assembly. [RS18A_YEAST] Located at the top of the head of the 40S subunit, it contacts several helices of the 18S rRNA (By similarity).[HAMAP-Rule:MF_01315] [RS14B_YEAST] Involved in nucleolar processing of pre-18S ribosomal RNA and ribosome assembly. [RS2_YEAST] Important in the assembly and function of the 40S ribosomal subunit. Mutations in this protein affects the control of translational fidelity. Involved in nucleolar processing of pre-18S ribosomal RNA and ribosome assembly. [RS7A_YEAST] Involved in nucleolar processing of pre-18S ribosomal RNA and ribosome assembly. [GBLP_YEAST] Located at the head of the 40S ribosomal subunit in the vicinity of the mRNA exit channel, it serves as a scaffold protein that can recruit other proteins to the ribosome. Involved in the negative regulation of translation of a specific subset of proteins. [RS19A_YEAST] Required for proper maturation of the small (40S) ribosomal subunit. Binds to 40s pre-ribosomal particles, probably required after association of NOC4 but before association of ENP1, TSR1 and RIO2 with 20/21S pre-rRNA. [RS6A_YEAST] Involved in nucleolar processing of pre-18S ribosomal RNA and ribosome assembly. [RS31_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). 40S ribosomal protein S31: 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. [RL4A_YEAST] Participates in the regulation of the accumulation of its own mRNA. [RL5_YEAST] Binds 5S RNA and is required for 60S subunit assembly. [RL25_YEAST] This protein binds to a specific region on the 26S rRNA. [RL11B_YEAST] Binds to 5S ribosomal RNA. Publication Abstract from PubMed Messenger RNA (mRNA) homeostasis represents an essential part of gene expression, in which the generation of mRNA by RNA polymerase is counter-balanced by its degradation by nucleases. The conserved 5'-to-3' exoribonuclease Xrn1 has a crucial role in eukaryotic mRNA homeostasis by degrading decapped or cleaved mRNAs post-translationally and, more surprisingly, also co-translationally. Here we report that active Xrn1 can directly and specifically interact with the translation machinery. A cryo-electron microscopy structure of a programmed Saccharomyces cerevisiae 80S ribosome-Xrn1 nuclease complex reveals how the conserved core of Xrn1 enables binding at the mRNA exit site of the ribosome. This interface provides a conduit for channelling of the mRNA from the ribosomal decoding site directly into the active center of the nuclease, thus separating mRNA decoding from degradation by only 17 +/- 1 nucleotides. These findings explain how rapid 5'-to-3' mRNA degradation is coupled efficiently to its final round of mRNA translation. Structure of the 80S ribosome-Xrn1 nuclease complex.,Tesina P, Heckel E, Cheng J, Fromont-Racine M, Buschauer R, Kater L, Beatrix B, Berninghausen O, Jacquier A, Becker T, Beckmann R Nat Struct Mol Biol. 2019 Mar 25. pii: 10.1038/s41594-019-0202-5. doi:, 10.1038/s41594-019-0202-5. PMID:30911188 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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