6p4h

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Structure of a mammalian small ribosomal subunit in complex with the Israeli Acute Paralysis Virus IRES (Class 2)

Structural highlights

6p4h is a 10 chain structure with sequence from Israeli acute paralysis virus and Oryctolagus cuniculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:Electron Microscopy, Resolution 3.2Å
Experimental data:Check to display Experimental Data
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

RSSA_RABIT Required for the assembly and/or stability of the 40S ribosomal subunit (PubMed:23873042, PubMed:25601755). Required for the processing of the 20S rRNA-precursor to mature 18S rRNA in a late step of the maturation of 40S ribosomal subunits (PubMed:23873042, PubMed:25601755). Also functions as a cell surface receptor for laminin (By similarity). Plays a role in cell adhesion to the basement membrane and in the consequent activation of signaling transduction pathways (By similarity). May play a role in cell fate determination and tissue morphogenesis (By similarity). Also acts as a receptor for several other ligands, including the pathogenic prion protein, viruses, and bacteria. Acts as a PPP1R16B-dependent substrate of PPP1CA (By similarity).[HAMAP-Rule:MF_03016][1] [2]

Publication Abstract from PubMed

Colony collapse disorder (CCD) is a multi-faceted syndrome decimating bee populations worldwide, and a group of viruses of the widely distributed Dicistroviridae family have been identified as a causing agent of CCD. This family of viruses employs non-coding RNA sequences, called internal ribosomal entry sites (IRESs), to precisely exploit the host machinery for viral protein production. Using single-particle cryo-electron microscopy (cryo-EM), we have characterized how the IRES of Israeli acute paralysis virus (IAPV) intergenic region captures and redirects translating ribosomes toward viral RNA messages. We reconstituted two in vitro reactions targeting a pre-translocation and a post-translocation state of the IAPV-IRES in the ribosome, allowing us to identify six structures using image processing classification methods. From these, we reconstructed the trajectory of IAPV-IRES from the early small subunit recruitment to the final post-translocated state in the ribosome. An early commitment of IRES/ribosome complexes for global pre-translocation mimicry explains the high efficiency observed for this IRES. Efforts directed toward fighting CCD by targeting the IAPV-IRES using RNA-interference technology are underway, and the structural framework presented here may assist in further refining these approaches.

The Israeli acute paralysis virus IRES captures host ribosomes by mimicking a ribosomal state with hybrid tRNAs.,Acosta-Reyes F, Neupane R, Frank J, Fernandez IS EMBO J. 2019 Oct 14:e102226. doi: 10.15252/embj.2019102226. PMID:31609474[3]

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

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See Also

References

  1. Lomakin IB, Steitz TA. The initiation of mammalian protein synthesis and mRNA scanning mechanism. Nature. 2013 Jul 21. doi: 10.1038/nature12355. PMID:23873042 doi:10.1038/nature12355
  2. Muhs M, Hilal T, Mielke T, Skabkin MA, Sanbonmatsu KY, Pestova TV, Spahn CM. Cryo-EM of Ribosomal 80S Complexes with Termination Factors Reveals the Translocated Cricket Paralysis Virus IRES. Mol Cell. 2015 Feb 5;57(3):422-432. doi: 10.1016/j.molcel.2014.12.016. Epub 2015 , Jan 15. PMID:25601755 doi:http://dx.doi.org/10.1016/j.molcel.2014.12.016
  3. Acosta-Reyes F, Neupane R, Frank J, Fernandez IS. The Israeli acute paralysis virus IRES captures host ribosomes by mimicking a ribosomal state with hybrid tRNAs. EMBO J. 2019 Oct 14:e102226. doi: 10.15252/embj.2019102226. PMID:31609474 doi:http://dx.doi.org/10.15252/embj.2019102226

Contents


6p4h, resolution 3.20Å

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