TY  - JOUR
AU  - Khawaja, Anas
AU  - Itoh, Yuzuru
AU  - Remes, Cristina
AU  - Spåhr, Henrik
AU  - Yukhnovets, Olessya
AU  - Höfig, Henning
AU  - Amunts, Alexey
AU  - Rorbach, Joanna
TI  - Distinct pre-initiation steps in human mitochondrial translation
JO  - Nature Communications
VL  - 11
IS  - 1
SN  - 2041-1723
CY  - [London]
PB  - Nature Publishing Group UK
M1  - FZJ-2020-02621
SP  - 2932
PY  - 2020
AB  - 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
LB  - PUB:(DE-HGF)16
C6  - pmid:32522994
UR  - <Go to ISI:>//WOS:000543969100003
DO  - DOI:10.1038/s41467-020-16503-2
UR  - https://juser.fz-juelich.de/record/878079
ER  -