Structures of the human mitochondrial ribosome bound to EF-G1 reveal distinct features of mitochondrial translation elongation

Ravi Kiran Koripella,Linda L Spremulli,Partha P Datta,Kalpana Bhargava,Manjuli R Sharma,Nilesh K Banavali,Rajendra K Agrawal,Pooja Keshavan,Prem S Kaushal

doi:10.1038/s41467-020-17715-2

Abstract

The mammalian mitochondrial ribosome (mitoribosome) and its associated translational factors have evolved to accommodate greater participation of proteins in mitochondrial translation. Here we present the 2.68–3.96 Å cryo-EM structures of the human 55S mitoribosome in complex with the human mitochondrial elongation factor G1 (EF-G1mt) in three distinct conformational states, including an intermediate state and a post-translocational state. These structures reveal the role of several mitochondria-specific (mito-specific) mitoribosomal proteins (MRPs) and a mito-specific segment of EF-G1mt in mitochondrial tRNA (tRNAmt) translocation. In particular, the mito-specific C-terminal extension in EF-G1mt is directly involved in translocation of the acceptor arm of the A-site tRNAmt. In addition to the ratchet-like and independent head-swiveling motions exhibited by the small mitoribosomal subunit, we discover significant conformational changes in MRP mL45 at the nascent polypeptide-exit site within the large mitoribosomal subunit that could be critical for tethering of the elongating mitoribosome onto the inner-mitochondrial membrane.

Highlights

The mammalian mitochondrial ribosome and its associated translational factors have evolved to accommodate greater participation of proteins in mitochondrial translation
Each of these steps are facilitated by translational factors that are homologous to their bacterial counterparts but carry mitochondria-specific segments[10,11]
The critical step of tRNA and mRNA translocation on the ribosome is promoted by elongation factor-G (EF-G) in eubacteria and homologous EF-2 in eukaryotic cytoplasm

Summary

Introduction

The mammalian mitochondrial ribosome (mitoribosome) and its associated translational factors have evolved to accommodate greater participation of proteins in mitochondrial translation. In the Class III complex, Domain IV makes contacts with multiple 12S rRNA components of the 28S subunit such as helix 24 (h24), h30, h44, and the anticodon arm of the tRNA bound in the P/P state (Fig. 3i).

Results

Conclusion