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000878079 1001_ $$0P:(DE-HGF)0$$aKhawaja, Anas$$b0
000878079 245__ $$aDistinct pre-initiation steps in human mitochondrial translation
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000878079 520__ $$aTranslation initiation in human mitochondria relies upon specialized mitoribosomes and initiation factors, mtIF2 and mtIF3, which have diverged from their bacterial counterparts. Here we report two distinct mitochondrial pre-initiation assembly steps involving those factors. Single-particle cryo-EM revealed that in the first step, interactions between mitochondria-specific protein mS37 and mtIF3 keep the small mitoribosomal subunit in a conformation favorable for a subsequent accommodation of mtIF2 in the second step. Combination with fluorescence cross-correlation spectroscopy analyses suggests that mtIF3 promotes complex assembly without mRNA or initiator tRNA binding, where exclusion is achieved by the N-terminal and C-terminal domains of mtIF3. Finally, the association of large mitoribosomal subunit is required for initiator tRNA and leaderless mRNA recruitment to form a stable initiation complex. These data reveal fundamental aspects of mammal
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000878079 7001_ $$00000-0001-7802-5572$$aItoh, Yuzuru$$b1
000878079 7001_ $$0P:(DE-Juel1)156351$$aRemes, Cristina$$b2
000878079 7001_ $$0P:(DE-HGF)0$$aSpåhr, Henrik$$b3
000878079 7001_ $$0P:(DE-Juel1)176889$$aYukhnovets, Olessya$$b4
000878079 7001_ $$0P:(DE-Juel1)165927$$aHöfig, Henning$$b5
000878079 7001_ $$00000-0002-5302-1740$$aAmunts, Alexey$$b6$$eCorresponding author
000878079 7001_ $$00000-0002-2891-2840$$aRorbach, Joanna$$b7$$eCorresponding author
000878079 773__ $$0PERI:(DE-600)2553671-0$$a10.1038/s41467-020-16503-2$$gVol. 11, no. 1, p. 2932$$n1$$p2932$$tNature Communications$$v11$$x2041-1723$$y2020
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