6n8o

Structural highlights

Function

[LSG1_YEAST] GTPase required for the nuclear export of the 60S ribosomal subunit. Acts by mediating the release of NMD3 from the 60S ribosomal subunit after export into the cytoplasm.^{[1] [2] [3] [4]} [RL11A_YEAST] Binds to 5S ribosomal RNA. [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).^{[5] [6]} [RL4A_YEAST] Participates in the regulation of the accumulation of its own mRNA.^[7] [RL37A_YEAST] Binds to the 23S rRNA (By similarity). [RL5_YEAST] Binds 5S RNA and is required for 60S subunit assembly. [NMD3_YEAST] Acts as an adapter for the XPO1/CRM1-mediated export of the 60S ribosomal subunit. Unlikely to play a significant role in nonsense-mediated mRNA decay (NMD).^[8] [PVH1_YEAST] May be directly involved in signal transduction and/or cell cycle regulation. It is necessary for maintaining growth rate or spore germination. Could show both activity toward tyrosine-protein phosphate as well as with serine-protein phosphate. [RL25_YEAST] This protein binds to a specific region on the 26S rRNA. [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.^{[9] [10] [11] [12] [13] [14]}

See Also

• Ribosome 3D structures

References

1. ↑ Hedges J, West M, Johnson AW. Release of the export adapter, Nmd3p, from the 60S ribosomal subunit requires Rpl10p and the cytoplasmic GTPase Lsg1p. EMBO J. 2005 Feb 9;24(3):567-79. Epub 2005 Jan 20. PMID:15660131 doi:http://dx.doi.org/7600547
2. ↑ West M, Hedges JB, Chen A, Johnson AW. Defining the order in which Nmd3p and Rpl10p load onto nascent 60S ribosomal subunits. Mol Cell Biol. 2005 May;25(9):3802-13. PMID:15831484 doi:http://dx.doi.org/25/9/3802
3. ↑ Hedges J, Chen YI, West M, Bussiere C, Johnson AW. Mapping the functional domains of yeast NMD3, the nuclear export adapter for the 60 S ribosomal subunit. J Biol Chem. 2006 Dec 1;281(48):36579-87. Epub 2006 Oct 2. PMID:17015443 doi:http://dx.doi.org/M606798200
4. ↑ Hofer A, Bussiere C, Johnson AW. Mutational analysis of the ribosomal protein Rpl10 from yeast. J Biol Chem. 2007 Nov 9;282(45):32630-9. Epub 2007 Aug 30. PMID:17761675 doi:http://dx.doi.org/10.1074/jbc.M705057200
5. ↑ 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
6. ↑ Ben-Shem A, Garreau de Loubresse N, Melnikov S, Jenner L, Yusupova G, Yusupov M. The structure of the eukaryotic ribosome at 3.0 A resolution. Science. 2011 Dec 16;334(6062):1524-9. Epub 2011 Nov 17. PMID:22096102 doi:10.1126/science.1212642
7. ↑ 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
8. ↑ Ho JH, Kallstrom G, Johnson AW. Nmd3p is a Crm1p-dependent adapter protein for nuclear export of the large ribosomal subunit. J Cell Biol. 2000 Nov 27;151(5):1057-66. PMID:11086007
9. ↑ Sanvito F, Piatti S, Villa A, Bossi M, Lucchini G, Marchisio PC, Biffo S. The beta4 integrin interactor p27(BBP/eIF6) is an essential nuclear matrix protein involved in 60S ribosomal subunit assembly. J Cell Biol. 1999 Mar 8;144(5):823-37. PMID:10085284
10. ↑ Senger B, Lafontaine DL, Graindorge JS, Gadal O, Camasses A, Sanni A, Garnier JM, Breitenbach M, Hurt E, Fasiolo F. The nucle(ol)ar Tif6p and Efl1p are required for a late cytoplasmic step of ribosome synthesis. Mol Cell. 2001 Dec;8(6):1363-73. PMID:11779510
11. ↑ Basu U, Si K, Warner JR, Maitra U. The Saccharomyces cerevisiae TIF6 gene encoding translation initiation factor 6 is required for 60S ribosomal subunit biogenesis. Mol Cell Biol. 2001 Mar;21(5):1453-62. PMID:11238882 doi:10.1128/MCB.21.5.1453-1462.2001
12. ↑ Menne TF, Goyenechea B, Sanchez-Puig N, Wong CC, Tonkin LM, Ancliff PJ, Brost RL, Costanzo M, Boone C, Warren AJ. The Shwachman-Bodian-Diamond syndrome protein mediates translational activation of ribosomes in yeast. Nat Genet. 2007 Apr;39(4):486-95. Epub 2007 Mar 11. PMID:17353896 doi:ng1994
13. ↑ Ray P, Basu U, Ray A, Majumdar R, Deng H, Maitra U. The Saccharomyces cerevisiae 60 S ribosome biogenesis factor Tif6p is regulated by Hrr25p-mediated phosphorylation. J Biol Chem. 2008 Apr 11;283(15):9681-91. doi: 10.1074/jbc.M710294200. Epub 2008 , Feb 5. PMID:18256024 doi:10.1074/jbc.M710294200
14. ↑ Groft CM, Beckmann R, Sali A, Burley SK. Crystal structures of ribosome anti-association factor IF6. Nat Struct Biol. 2000 Dec;7(12):1156-64. PMID:11101899 doi:10.1038/82017
15. ↑ Zhou Y, Musalgaonkar S, Johnson AW, Taylor DW. Tightly-orchestrated rearrangements govern catalytic center assembly of the ribosome. Nat Commun. 2019 Feb 27;10(1):958. doi: 10.1038/s41467-019-08880-0. PMID:30814529 doi:http://dx.doi.org/10.1038/s41467-019-08880-0