Publication Abstract from PubMed
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-tRNAiMet). 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-tRNAiMet-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-tRNAiMet to the 60S P site and redefines the role of eIF5B as a tRNA-reorientation factor.
Structure of the mammalian 80S initiation complex with initiation factor 5B on HCV-IRES RNA.,Yamamoto H, Unbehaun A, Loerke J, Behrmann E, Collier M, Burger J, Mielke T, Spahn CM Nat Struct Mol Biol. 2014 Aug;21(8):721-727. doi: 10.1038/nsmb.2859. Epub 2014, Jul 27. PMID:25064512[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
