Structure of the Mammalian 80S Initiation Complex with Initiation Factor 5B on HCV-IRES RNA

Overview

Journal Nat Struct Mol Biol

Specialties Cell Biology
Molecular Biology

Date 2014 Jul 28

PMID 25064512

Citations 68

Authors

Hiroshi Yamamoto

Anett Unbehaun

Justus Loerke

Elmar Behrmann

Marianne Collier

Jorg Burger

Thorsten Mielke

Christian M T Spahn

Affiliations

Soon will be listed here.

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.

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