Nmd3 is a structural mimic of eIF5A, and activates the cpGTPase Lsg1 during 60S ribosome biogenesis: 60S-Nmd3 ComplexNmd3 is a structural mimic of eIF5A, and activates the cpGTPase Lsg1 during 60S ribosome biogenesis: 60S-Nmd3 Complex

Structural highlights

5t6r is a 45 chain structure with sequence from methanococcus_frisius_blotevogel_et_al._1986 Atcc 43340 methanococcus frisius blotevogel et al. 1986, Baker's yeast and Saccharomyces cerevisiae. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:,
NonStd Res:
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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

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[4]

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

References

  1. 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
  2. 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
  3. 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
  4. 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

5t6r, resolution 4.50Å

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