| 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] [RL11B_YEAST] Binds to 5S ribosomal RNA. [RL4A_YEAST] Participates in the regulation of the accumulation of its own mRNA.[6] [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] [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.[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] [RLA0_YEAST] Ribosomal protein P0 is the functional equivalent of E.coli protein L10. [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] [IF5A1_YEAST] mRNA-binding protein involved in translation elongation. Has an important function at the level of mRNA turnover, probably acting downstream of decapping. Involved in actin dynamics and cell cycle progression, mRNA decay and probably in a pathway involved in stress response and maintenance of cell wall integrity. Essential for polarized growth, a process necessary for G1/S transition. May mediate large range of effects of the polyamine spermidine in the cell.[13] [14] [15] [16] [17] [18] [19] [20] [21] [RS7A_YEAST] Involved in nucleolar processing of pre-18S ribosomal RNA and ribosome assembly.[22] [RS6A_YEAST] Involved in nucleolar processing of pre-18S ribosomal RNA and ribosome assembly.[23] [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.[24] [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.[25]
Publication Abstract from PubMed
Eukaryotic translation initiation factor eIF5A promotes protein synthesis by resolving polyproline-induced ribosomal stalling. Here we report a 3.25A-resolution crystal structure of eIF5A bound to the yeast 80S ribosome. The structure reveals a previously unseen conformation of an eIF5A-ribosome complex and highlights a possible functional link between conformational changes of the ribosome during protein synthesis and the eIF5A-ribosome association.
Crystal structure of hypusine-containing translation factor eIF5A bound to a rotated eukaryotic ribosome.,Melnikov S, Mailliot J, Shin BS, Rigger L, Yusupova G, Micura R, Dever TE, Yusupov M J Mol Biol. 2016 May 16. pii: S0022-2836(16)30154-1. doi:, 10.1016/j.jmb.2016.05.011. PMID:27196944[26]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Leger-Silvestre I, Caffrey JM, Dawaliby R, Alvarez-Arias DA, Gas N, Bertolone SJ, Gleizes PE, Ellis SR. Specific Role for Yeast Homologs of the Diamond Blackfan Anemia-associated Rps19 Protein in Ribosome Synthesis. J Biol Chem. 2005 Nov 18;280(46):38177-85. Epub 2005 Sep 12. PMID:16159874 doi:http://dx.doi.org/10.1074/jbc.M506916200
- ↑ Gregory LA, Aguissa-Toure AH, Pinaud N, Legrand P, Gleizes PE, Fribourg S. Molecular basis of Diamond-Blackfan anemia: structure and function analysis of RPS19. Nucleic Acids Res. 2007;35(17):5913-21. Epub 2007 Aug 28. PMID:17726054 doi:10.1093/nar/gkm626
- ↑ Bernstein KA, Gallagher JE, Mitchell BM, Granneman S, Baserga SJ. The small-subunit processome is a ribosome assembly intermediate. Eukaryot Cell. 2004 Dec;3(6):1619-26. PMID:15590835 doi:http://dx.doi.org/10.1128/EC.3.6.1619-1626.2004
- ↑ Van Dyke MW, Nelson LD, Weilbaecher RG, Mehta DV. Stm1p, a G4 quadruplex and purine motif triplex nucleic acid-binding protein, interacts with ribosomes and subtelomeric Y' DNA in Saccharomyces cerevisiae. J Biol Chem. 2004 Jun 4;279(23):24323-33. Epub 2004 Mar 23. PMID:15044472 doi:http://dx.doi.org/10.1074/jbc.M401981200
- ↑ Bernstein KA, Gallagher JE, Mitchell BM, Granneman S, Baserga SJ. The small-subunit processome is a ribosome assembly intermediate. Eukaryot Cell. 2004 Dec;3(6):1619-26. PMID:15590835 doi:http://dx.doi.org/10.1128/EC.3.6.1619-1626.2004
- ↑ Presutti C, Ciafre SA, Bozzoni I. The ribosomal protein L2 in S. cerevisiae controls the level of accumulation of its own mRNA. EMBO J. 1991 Aug;10(8):2215-21. PMID:2065661
- ↑ Lee AS, Burdeinick-Kerr R, Whelan SP. A ribosome-specialized translation initiation pathway is required for cap-dependent translation of vesicular stomatitis virus mRNAs. Proc Natl Acad Sci U S A. 2013 Jan 2;110(1):324-9. doi: 10.1073/pnas.1216454109. , Epub 2012 Nov 19. PMID:23169626 doi:http://dx.doi.org/10.1073/pnas.1216454109
- ↑ Lee AS, Burdeinick-Kerr R, Whelan SP. A ribosome-specialized translation initiation pathway is required for cap-dependent translation of vesicular stomatitis virus mRNAs. Proc Natl Acad Sci U S A. 2013 Jan 2;110(1):324-9. doi: 10.1073/pnas.1216454109. , Epub 2012 Nov 19. PMID:23169626 doi:http://dx.doi.org/10.1073/pnas.1216454109
- ↑ Leger-Silvestre I, Milkereit P, Ferreira-Cerca S, Saveanu C, Rousselle JC, Choesmel V, Guinefoleau C, Gas N, Gleizes PE. The ribosomal protein Rps15p is required for nuclear exit of the 40S subunit precursors in yeast. EMBO J. 2004 Jun 16;23(12):2336-47. Epub 2004 May 27. PMID:15167894 doi:http://dx.doi.org/10.1038/sj.emboj.7600252
- ↑ Ford CL, Randal-Whitis L, Ellis SR. Yeast proteins related to the p40/laminin receptor precursor are required for 20S ribosomal RNA processing and the maturation of 40S ribosomal subunits. Cancer Res. 1999 Feb 1;59(3):704-10. PMID:9973221
- ↑ Tabb-Massey A, Caffrey JM, Logsden P, Taylor S, Trent JO, Ellis SR. Ribosomal proteins Rps0 and Rps21 of Saccharomyces cerevisiae have overlapping functions in the maturation of the 3' end of 18S rRNA. Nucleic Acids Res. 2003 Dec 1;31(23):6798-805. PMID:14627813
- ↑ Tabb-Massey A, Caffrey JM, Logsden P, Taylor S, Trent JO, Ellis SR. Ribosomal proteins Rps0 and Rps21 of Saccharomyces cerevisiae have overlapping functions in the maturation of the 3' end of 18S rRNA. Nucleic Acids Res. 2003 Dec 1;31(23):6798-805. PMID:14627813
- ↑ Lee YB, Joe YA, Wolff EC, Dimitriadis EK, Park MH. Complex formation between deoxyhypusine synthase and its protein substrate, the eukaryotic translation initiation factor 5A (eIF5A) precursor. Biochem J. 1999 May 15;340 ( Pt 1):273-81. PMID:10229683
- ↑ Zanelli CF, Valentini SR. Pkc1 acts through Zds1 and Gic1 to suppress growth and cell polarity defects of a yeast eIF5A mutant. Genetics. 2005 Dec;171(4):1571-81. Epub 2005 Sep 12. PMID:16157662 doi:http://dx.doi.org/genetics.105.048082
- ↑ Chatterjee I, Gross SR, Kinzy TG, Chen KY. Rapid depletion of mutant eukaryotic initiation factor 5A at restrictive temperature reveals connections to actin cytoskeleton and cell cycle progression. Mol Genet Genomics. 2006 Mar;275(3):264-76. Epub 2006 Jan 12. PMID:16408210 doi:http://dx.doi.org/10.1007/s00438-005-0086-4
- ↑ Zanelli CF, Maragno AL, Gregio AP, Komili S, Pandolfi JR, Mestriner CA, Lustri WR, Valentini SR. eIF5A binds to translational machinery components and affects translation in yeast. Biochem Biophys Res Commun. 2006 Oct 6;348(4):1358-66. Epub 2006 Aug 7. PMID:16914118 doi:http://dx.doi.org/10.1016/j.bbrc.2006.07.195
- ↑ Gregio AP, Cano VP, Avaca JS, Valentini SR, Zanelli CF. eIF5A has a function in the elongation step of translation in yeast. Biochem Biophys Res Commun. 2009 Mar 20;380(4):785-90. Epub 2009 Jan 29. PMID:19338753 doi:http://dx.doi.org/S0006-291X(09)00203-4
- ↑ Saini P, Eyler DE, Green R, Dever TE. Hypusine-containing protein eIF5A promotes translation elongation. Nature. 2009 May 7;459(7243):118-21. PMID:19424157 doi:http://dx.doi.org/nature08034
- ↑ Benne R, Hershey JW. The mechanism of action of protein synthesis initiation factors from rabbit reticulocytes. J Biol Chem. 1978 May 10;253(9):3078-87. PMID:641056
- ↑ Kang HA, Hershey JW. Effect of initiation factor eIF-5A depletion on protein synthesis and proliferation of Saccharomyces cerevisiae. J Biol Chem. 1994 Feb 11;269(6):3934-40. PMID:8307948
- ↑ Zuk D, Jacobson A. A single amino acid substitution in yeast eIF-5A results in mRNA stabilization. EMBO J. 1998 May 15;17(10):2914-25. PMID:9582285 doi:http://dx.doi.org/10.1093/emboj/17.10.2914
- ↑ Bernstein KA, Gallagher JE, Mitchell BM, Granneman S, Baserga SJ. The small-subunit processome is a ribosome assembly intermediate. Eukaryot Cell. 2004 Dec;3(6):1619-26. PMID:15590835 doi:http://dx.doi.org/10.1128/EC.3.6.1619-1626.2004
- ↑ Bernstein KA, Gallagher JE, Mitchell BM, Granneman S, Baserga SJ. The small-subunit processome is a ribosome assembly intermediate. Eukaryot Cell. 2004 Dec;3(6):1619-26. PMID:15590835 doi:http://dx.doi.org/10.1128/EC.3.6.1619-1626.2004
- ↑ Bernstein KA, Gallagher JE, Mitchell BM, Granneman S, Baserga SJ. The small-subunit processome is a ribosome assembly intermediate. Eukaryot Cell. 2004 Dec;3(6):1619-26. PMID:15590835 doi:http://dx.doi.org/10.1128/EC.3.6.1619-1626.2004
- ↑ Gerbasi VR, Weaver CM, Hill S, Friedman DB, Link AJ. Yeast Asc1p and mammalian RACK1 are functionally orthologous core 40S ribosomal proteins that repress gene expression. Mol Cell Biol. 2004 Sep;24(18):8276-87. PMID:15340087 doi:10.1128/MCB.24.18.8276-8287.2004
- ↑ Melnikov S, Mailliot J, Shin BS, Rigger L, Yusupova G, Micura R, Dever TE, Yusupov M. Crystal structure of hypusine-containing translation factor eIF5A bound to a rotated eukaryotic ribosome. J Mol Biol. 2016 May 16. pii: S0022-2836(16)30154-1. doi:, 10.1016/j.jmb.2016.05.011. PMID:27196944 doi:http://dx.doi.org/10.1016/j.jmb.2016.05.011
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