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From Proteopedia
Structure of the anisomycin-containing uL3 W255C mutant 80S yeast ribosome
Structural highlights
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Function[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). [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.[1] [2] [RS14A_YEAST] Involved in nucleolar processing of pre-18S ribosomal RNA and ribosome assembly.[3] [RL25_YEAST] This protein binds to a specific region on the 26S rRNA. [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] [STM1_YEAST] Binds specifically G4 quadruplex (these are four-stranded right-handed helices, stabilized by guanine base quartets) and purine motif triplex (characterized by a third, antiparallel purine-rich DNA strand located within the major groove of a homopurine stretch of duplex DNA) nucleic acid structures. These structures may be present at telomeres or in rRNAs. Acts with CDC13 to control telomere length homeostasis. Involved in the control of the apoptosis-like cell death.[4] [RS9A_YEAST] Involved in nucleolar processing of pre-18S ribosomal RNA and ribosome assembly.[5] [RL11A_YEAST] Binds to 5S ribosomal RNA. [RL4A_YEAST] Participates in the regulation of the accumulation of its own mRNA.[6] [RLA0_YEAST] Ribosomal protein P0 is the functional equivalent of E.coli protein L10. [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).[7] 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.[8] [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.[9] [10] [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.[11] [RL5_YEAST] Binds 5S RNA and is required for 60S subunit assembly. [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.[12] [RS7A_YEAST] Involved in nucleolar processing of pre-18S ribosomal RNA and ribosome assembly.[13] [RS6A_YEAST] Involved in nucleolar processing of pre-18S ribosomal RNA and ribosome assembly.[14] [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.[15] [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.[16] Publication Abstract from PubMedThe ribosome has been described as a ribozyme in which ribosomal RNA is responsible for peptidyl-transferase reaction catalysis. The W255C mutation of the universally conserved ribosomal protein uL3 has diverse effects on ribosome function (e.g., increased affinities for transfer RNAs, decreased rates of peptidyl-transfer), and cells harboring this mutation are resistant to peptidyl-transferase inhibitors (e.g., anisomycin). These observations beg the question of how a single amino acid mutation may have such wide ranging consequences. Here, we report the structure of the vacant yeast uL3 W255C mutant ribosome by X-ray crystallography, showing a disruption of the A-site side of the peptidyl-transferase center (PTC). An additional X-ray crystallographic structure of the anisomycin-containing mutant ribosome shows that high concentrations of this inhibitor restore a "WT-like" configuration to this region of the PTC, providing insight into the resistance mechanism of the mutant. Globally, our data demonstrate that ribosomal protein uL3 is structurally essential to ensure an optimal and catalytically efficient organization of the PTC, highlighting the importance of proteins in the RNA-centered ribosome. Crystal Structures of the uL3 Mutant Ribosome: Illustration of the Importance of Ribosomal Proteins for Translation Efficiency.,Mailliot J, Garreau de Loubresse N, Yusupova G, Meskauskas A, Dinman JD, Yusupov M J Mol Biol. 2016 Feb 18. pii: S0022-2836(16)00129-7. doi:, 10.1016/j.jmb.2016.02.013. PMID:26906928[17] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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