%0 Journal Article
%A Khawaja, Anas
%A Itoh, Yuzuru
%A Remes, Cristina
%A Spåhr, Henrik
%A Yukhnovets, Olessya
%A Höfig, Henning
%A Amunts, Alexey
%A Rorbach, Joanna
%T Distinct pre-initiation steps in human mitochondrial translation
%J Nature Communications
%V 11
%N 1
%@ 2041-1723
%C [London]
%I Nature Publishing Group UK
%M FZJ-2020-02621
%P 2932
%D 2020
%X Translation initiation in human mitochondria relies upon specialized mitoribosomes and initiation factors, mtIF2 and mtIF3, which have diverged from their bacterial counterparts. Here we report two distinct mitochondrial pre-initiation assembly steps involving those factors. Single-particle cryo-EM revealed that in the first step, interactions between mitochondria-specific protein mS37 and mtIF3 keep the small mitoribosomal subunit in a conformation favorable for a subsequent accommodation of mtIF2 in the second step. Combination with fluorescence cross-correlation spectroscopy analyses suggests that mtIF3 promotes complex assembly without mRNA or initiator tRNA binding, where exclusion is achieved by the N-terminal and C-terminal domains of mtIF3. Finally, the association of large mitoribosomal subunit is required for initiator tRNA and leaderless mRNA recruitment to form a stable initiation complex. These data reveal fundamental aspects of mammal
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:32522994
%U <Go to ISI:>//WOS:000543969100003
%R 10.1038/s41467-020-16503-2
%U https://juser.fz-juelich.de/record/878079