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100 1 _ |a Khawaja, Anas
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245 _ _ |a Distinct pre-initiation steps in human mitochondrial translation
260 _ _ |a [London]
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520 _ _ |a 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
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700 1 _ |a Itoh, Yuzuru
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700 1 _ |a Remes, Cristina
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700 1 _ |a Spåhr, Henrik
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700 1 _ |a Yukhnovets, Olessya
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700 1 _ |a Höfig, Henning
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700 1 _ |a Amunts, Alexey
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700 1 _ |a Rorbach, Joanna
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773 _ _ |a 10.1038/s41467-020-16503-2
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