6rw4 | pdb_00006rw4
Structure of human mitochondrial 28S ribosome in complex with mitochondrial IF3
Structural highlights
Disease[RT22_HUMAN] Hypotonia with lactic acidemia and hyperammonemia. The disease is caused by mutations affecting the gene represented in this entry. [RT16_HUMAN] Combined oxidative phosphorylation defect type 2. The disease is caused by mutations affecting the gene represented in this entry. Function[IF3M_HUMAN] IF-3 binds to the 28S ribosomal subunit and shifts the equilibrum between 55S ribosomes and their 39S and 28S subunits in favor of the free subunits, thus enhancing the availability of 28S subunits on which protein synthesis initiation begins.[1] [AKIP_HUMAN] May act as a negative regulator of Aurora-A kinase, by down-regulation through proteasome-dependent degradation. [RT29_HUMAN] Involved in mediating interferon-gamma-induced cell death. [PTCD3_HUMAN] Mitochondrial RNA-binding protein that has a role in mitochondrial translation.[2] Publication Abstract from PubMedTranslation 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 mammalian protein synthesis that are specific to mitochondria. Distinct pre-initiation steps in human mitochondrial translation.,Khawaja A, Itoh Y, Remes C, Spahr H, Yukhnovets O, Hofig H, Amunts A, Rorbach J Nat Commun. 2020 Jun 10;11(1):2932. doi: 10.1038/s41467-020-16503-2. PMID:32522994[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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