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Nat Struct Mol Biol. 2014 Aug;21(8):721-7. doi: 10.1038/nsmb.2859. Epub 2014 Jul 27.

Structure of the mammalian 80S initiation complex with initiation factor 5B on HCV-IRES RNA.

Author information

1
1] Institute of Medical Physics and Biophysics, Charité-Universitätsmedizin, Berlin, Germany. [2].
2
Institute of Medical Physics and Biophysics, Charité-Universitätsmedizin, Berlin, Germany.
3
1] Institute of Medical Physics and Biophysics, Charité-Universitätsmedizin, Berlin, Germany. [2] UltraStrukturNetzwerk, Max Planck Institute for Molecular Genetics, Berlin, Germany.

Abstract

The universally conserved eukaryotic initiation factor (eIF) 5B, a translational GTPase, is essential for canonical translation initiation. It is also required for initiation facilitated by the internal ribosomal entry site (IRES) of hepatitis C virus (HCV) RNA. eIF5B promotes joining of 60S ribosomal subunits to 40S ribosomal subunits bound by initiator tRNA (Met-tRNAi(Met)). However, the exact molecular mechanism by which eIF5B acts has not been established. Here we present cryo-EM reconstructions of the mammalian 80S-HCV-IRES-Met-tRNAi(Met)-eIF5B-GMPPNP complex. We obtained two substates distinguished by the rotational state of the ribosomal subunits and the configuration of initiator tRNA in the peptidyl (P) site. Accordingly, a combination of conformational changes in the 80S ribosome and in initiator tRNA facilitates binding of the Met-tRNAi(Met) to the 60S P site and redefines the role of eIF5B as a tRNA-reorientation factor.

PMID:
25064512
DOI:
10.1038/nsmb.2859
[Indexed for MEDLINE]

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