5m1j
From Proteopedia
Nonstop ribosomal complex bound with Dom34 and Hbs1
Structural highlights
Function[HBS1_YEAST] Involved in protein translation. Together with DOM34, may function in recognizing stalled ribosomes and triggering endonucleolytic cleavage of the mRNA, a mechanism to release non-functional ribosomes and degrade damaged mRNAs.[1] [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] [RL4A_YEAST] Participates in the regulation of the accumulation of its own mRNA.[2] [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.[3] [4] [RL37A_YEAST] Binds to the 23S rRNA (By similarity). [RL401_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).[5] 60S ribosomal protein L40: component of the 60S subunit of the ribosome. Ribosomal protein L40 is essential for translation of a subset of cellular transcripts, including stress response transcripts, such as DDR2.[6] [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). [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.[7] [RS7A_YEAST] Involved in nucleolar processing of pre-18S ribosomal RNA and ribosome assembly.[8] [RL11A_YEAST] Binds to 5S ribosomal RNA. [RL5_YEAST] Binds 5S RNA and is required for 60S subunit assembly. [RS9A_YEAST] Involved in nucleolar processing of pre-18S ribosomal RNA and ribosome assembly.[9] [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.[10] [11] [DOM34_YEAST] Involved in protein translation. Together with HBS1, may function in recognizing stalled ribosomes and triggering endonucleolytic cleavage of the mRNA, a mechanism to release non-functional ribosomes and degrade damaged mRNAs. The complex formed by DOM34 and HBS1 has ribonuclease activity towards double-stranded RNA substrates, but does not cleave single-stranded RNA. Acts as endonuclease; has no exonuclease activity. Increases the affinity of HBS1 for GTP, but nor for GDP. Promotes G1 progression and differentiation and is involved in mitotic and meiotic cell divisions.[12] [13] [14] [RL25_YEAST] This protein binds to a specific region on the 26S rRNA. [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.[15] [RS14A_YEAST] Involved in nucleolar processing of pre-18S ribosomal RNA and ribosome assembly.[16] [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.[17] [RS6A_YEAST] Involved in nucleolar processing of pre-18S ribosomal RNA and ribosome assembly.[18] [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.[19] Publication Abstract from PubMedThe surveillance of mRNA translation is imperative for homeostasis. Monitoring the integrity of the message is essential, as the translation of aberrant mRNAs leads to stalling of the translational machinery. During ribosomal rescue, arrested ribosomes are specifically recognized by the conserved eukaryotic proteins Dom34 and Hbs1, to initiate their recycling. Here we solve the structure of Dom34 and Hbs1 bound to a yeast ribosome programmed with a nonstop mRNA at 3.3 A resolution using cryo-electron microscopy. The structure shows that Domain N of Dom34 is inserted into the upstream mRNA-binding groove via direct stacking interactions with conserved nucleotides of 18S rRNA. It senses the absence of mRNA at the A-site and part of the mRNA entry channel by direct competition. Thus, our analysis establishes the structural foundation for the recognition of aberrantly stalled 80S ribosomes by the Dom34.Hbs1.GTP complex during Dom34-mediated mRNA surveillance pathways. Structural insights into ribosomal rescue by Dom34 and Hbs1 at near-atomic resolution.,Hilal T, Yamamoto H, Loerke J, Burger J, Mielke T, Spahn CM Nat Commun. 2016 Dec 20;7:13521. doi: 10.1038/ncomms13521. PMID:27995908[20] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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