8ipy

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human nuclear pre-60S ribosomal particle - State D'

Structural highlights

8ipy is a 10 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:Electron Microscopy, Resolution 3.2Å
Ligands:2MG, 5MC, 5MU, 6MZ, 7MG, A2M, B8K, B8Q, B8T, B8W, B9B, B9H, BGH, E7G, GTP, I4U, M7A, MG, N, OMC, OMG, OMU, P4U, P7G, UR3
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

IF6_HUMAN Binds to the 60S ribosomal subunit and prevents its association with the 40S ribosomal subunit to form the 80S initiation complex in the cytoplasm (PubMed:10085284, PubMed:14654845, PubMed:21536732, PubMed:32669547). Behaves as a stimulatory translation initiation factor downstream insulin/growth factors. 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 a RACK1 (RACK1)-dependent protein kinase C activity (PubMed:10085284, PubMed:14654845, PubMed:21536732). In tissues responsive to insulin, controls fatty acid synthesis and glycolysis by exerting translational control of adipogenic transcription factors such as CEBPB, CEBPD and ATF4 that have G/C rich or uORF in their 5'UTR. Required for ROS-dependent megakaryocyte maturation and platelets formation, controls the expression of mitochondrial respiratory chain genes involved in reactive oxygen species (ROS) synthesis (By similarity). Involved in miRNA-mediated gene silencing by the RNA-induced silencing complex (RISC). Required for both miRNA-mediated translational repression and miRNA-mediated cleavage of complementary mRNAs by RISC (PubMed:17507929). Modulates cell cycle progression and global translation of pre-B cells, its activation seems to be rate-limiting in tumorigenesis and tumor growth (By similarity).[HAMAP-Rule:MF_03132][1] [2] [3] [4] [5]

Publication Abstract from PubMed

Eukaryotic ribosome assembly is a highly orchestrated process that involves over two hundred protein factors. After early assembly events on nascent rRNA in the nucleolus, pre-60S particles undergo continuous maturation steps in the nucleoplasm, and prepare for nuclear export. Here, we report eleven cryo-EM structures of the nuclear pre-60S particles isolated from human cells through epitope-tagged GNL2, at resolutions of 2.8-4.3 A. These high-resolution snapshots provide fine details for several major structural remodeling events at a virtual temporal resolution. Two new human nuclear factors, L10K and C11orf98, were also identified. Comparative structural analyses reveal that many assembly factors act as successive place holders to control the timing of factor association/dissociation events. They display multi-phasic binding properties for different domains and generate complex binding inter-dependencies as a means to guide the rRNA maturation process towards its mature conformation. Overall, our data reveal that nuclear assembly of human pre-60S particles is generally hierarchical with short branch pathways, and a few factors display specific roles as rRNA chaperones by confining rRNA helices locally to facilitate their folding, such as the C-terminal domain of SDAD1.

Visualizing the nucleoplasmic maturation of human pre-60S ribosomal particles.,Zhang Y, Liang X, Luo S, Chen Y, Li Y, Ma C, Li N, Gao N Cell Res. 2023 Jul 25. doi: 10.1038/s41422-023-00853-9. PMID:37491604[6]

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

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Citations
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Structural insights into coordinating 5S RNP rotation with ITS2 pre-RNA processing during ribosome formation.
Thoms et al. (2023)
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See Also

References

  1. ↑ 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
  2. ↑ Ceci M, Gaviraghi C, Gorrini C, Sala LA, Offenhäuser N, Marchisio PC, Biffo S. Release of eIF6 (p27BBP) from the 60S subunit allows 80S ribosome assembly. Nature. 2003 Dec 4;426(6966):579-84. PMID:14654845 doi:10.1038/nature02160
  3. ↑ Chendrimada TP, Finn KJ, Ji X, Baillat D, Gregory RI, Liebhaber SA, Pasquinelli AE, Shiekhattar R. MicroRNA silencing through RISC recruitment of eIF6. Nature. 2007 Jun 14;447(7146):823-8. Epub 2007 May 16. PMID:17507929 doi:http://dx.doi.org/10.1038/nature05841
  4. ↑ Finch AJ, Hilcenko C, Basse N, Drynan LF, Goyenechea B, Menne TF, Gonzalez Fernandez A, Simpson P, D'Santos CS, Arends MJ, Donadieu J, Bellanne-Chantelot C, Costanzo M, Boone C, McKenzie AN, Freund SM, Warren AJ. Uncoupling of GTP hydrolysis from eIF6 release on the ribosome causes Shwachman-Diamond syndrome. Genes Dev. 2011 May 1;25(9):917-29. PMID:21536732 doi:10.1101/gad.623011
  5. ↑ Liang X, Zuo MQ, Zhang Y, Li N, Ma C, Dong MQ, Gao N. Structural snapshots of human pre-60S ribosomal particles before and after nuclear export. Nat Commun. 2020 Jul 15;11(1):3542. PMID:32669547 doi:10.1038/s41467-020-17237-x
  6. ↑ Zhang Y, Liang X, Luo S, Chen Y, Li Y, Ma C, Li N, Gao N. Visualizing the nucleoplasmic maturation of human pre-60S ribosomal particles. Cell Res. 2023 Jul 25. PMID:37491604 doi:10.1038/s41422-023-00853-9

Contents


PDB ID 8ipy

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