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5t62

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Revision as of 10:33, 8 November 2017

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Nmd3 is a structural mimic of eIF5A, and activates the cpGTPase Lsg1 during 60S ribosome biogenesis: 60S-Nmd3-Tif6-Lsg1 Complex

Structural highlights

5t62 is a 47 chain structure with sequence from Atcc 18824, Baker's yeast, Saccharomyces cerevisiae and Saccharomyces cerevisiae s288c. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, ,
NonStd Res:	,
Related:	5t6r
Gene:	TIF6, CDC95, YPR016C, LPZ15C (Baker's yeast)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Warning: this is a large structure, and loading might take a long time or not happen at all.

Function

[RL4A_YEAST] Participates in the regulation of the accumulation of its own mRNA.^[1] [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.^[2] ^[3] ^[4] ^[5] ^[6] ^[7] [RL25_YEAST] This protein binds to a specific region on the 26S rRNA. [RL11A_YEAST] Binds to 5S ribosomal RNA. [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).^[8] 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.^[9] [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).^[10] [RL37A_YEAST] Binds to the 23S rRNA (By similarity). [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.^[11] ^[12] ^[13] ^[14] [RL5_YEAST] Binds 5S RNA and is required for 60S subunit assembly.

Publication Abstract from PubMed

During ribosome biogenesis in eukaryotes, nascent subunits are exported to the cytoplasm in a functionally inactive state. 60S subunits are activated through a series of cytoplasmic maturation events. The last known events in the cytoplasm are the release of Tif6 by Efl1 and Sdo1 and the release of the export adapter, Nmd3, by the GTPase Lsg1. Here, we have used cryo-electron microscopy to determine the structure of the 60S subunit bound by Nmd3, Lsg1, and Tif6. We find that a central domain of Nmd3 mimics the translation elongation factor eIF5A, inserting into the E site of the ribosome and pulling the L1 stalk into a closed position. Additional domains occupy the P site and extend toward the sarcin-ricin loop to interact with Tif6. Nmd3 and Lsg1 together embrace helix 69 of the B2a intersubunit bridge, inducing base flipping that we suggest may activate the GTPase activity of Lsg1.

Nmd3 is a structural mimic of eIF5A, and activates the cpGTPase Lsg1 during 60S ribosome biogenesis.,Malyutin AG, Musalgaonkar S, Patchett S, Frank J, Johnson AW EMBO J. 2017 Feb 8. pii: e201696012. doi: 10.15252/embj.201696012. PMID:28179369^[15]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ 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
↑ 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
↑ 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
↑ 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
↑ 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
↑ 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
↑ 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
↑ 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
↑ 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
↑ 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
↑ 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
↑ 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
↑ 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
↑ Malyutin AG, Musalgaonkar S, Patchett S, Frank J, Johnson AW. Nmd3 is a structural mimic of eIF5A, and activates the cpGTPase Lsg1 during 60S ribosome biogenesis. EMBO J. 2017 Feb 8. pii: e201696012. doi: 10.15252/embj.201696012. PMID:28179369 doi:http://dx.doi.org/10.15252/embj.201696012

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5t62"

@@ Line 3: / Line 3: @@
 <StructureSection load='5t62' size='340' side='right' caption='[[5t62]], [[Resolution|resolution]] 3.30&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5t62]] is a 47 chain structure with sequence from [http://en.wikipedia.org/wiki/ ], [http://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae], [http://en.wikipedia.org/wiki/Saccharomyces_cerevisiae_(strain_atcc_204508_/_s288c) Saccharomyces cerevisiae (strain atcc 204508 / s288c)] and [http://en.wikipedia.org/wiki/Saccharomyces_cerevisiae_s288c Saccharomyces cerevisiae s288c]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5T62 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5T62 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5t62]] is a 47 chain structure with sequence from [http://en.wikipedia.org/wiki/Atcc_18824 Atcc 18824], [http://en.wikipedia.org/wiki/Baker's_yeast Baker's yeast], [http://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae] and [http://en.wikipedia.org/wiki/Saccharomyces_cerevisiae_s288c Saccharomyces cerevisiae s288c]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5T62 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5T62 FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GNP:PHOSPHOAMINOPHOSPHONIC+ACID-GUANYLATE+ESTER'>GNP</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
 <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=PSU:PSEUDOURIDINE-5-MONOPHOSPHATE'>PSU</scene>, <scene name='pdbligand=UNK:UNKNOWN'>UNK</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5t6r|5t6r]]</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TIF6, CDC95, YPR016C, LPZ15C ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=559292 Baker's yeast])</td></tr>
 <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5t62 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5t62 OCA], [http://pdbe.org/5t62 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5t62 RCSB], [http://www.ebi.ac.uk/pdbsum/5t62 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5t62 ProSAT]</span></td></tr>
 </table>
@@ Line 25: / Line 26: @@
 __TOC__
 </StructureSection>
+[[Category: Atcc 18824]]
+[[Category: Baker's yeast]]
 [[Category: Saccharomyces cerevisiae]]
 [[Category: Saccharomyces cerevisiae s288c]]

5t62

From Proteopedia

Revision as of 10:33, 8 November 2017

Nmd3 is a structural mimic of eIF5A, and activates the cpGTPase Lsg1 during 60S ribosome biogenesis: 60S-Nmd3-Tif6-Lsg1 Complex

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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