Structural highlights
6rw4 is a 31 chain structure with sequence from Human and Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
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| Ligands: | , , , , , , , , |
| NonStd Res: | , , , , |
| Gene: | MTIF3, DC38 (HUMAN) |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
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 PubMed
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 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
- ↑ Koc EC, Spremulli LL. Identification of mammalian mitochondrial translational initiation factor 3 and examination of its role in initiation complex formation with natural mRNAs. J Biol Chem. 2002 Sep 20;277(38):35541-9. doi: 10.1074/jbc.M202498200. Epub 2002 , Jul 2. PMID:12095986 doi:http://dx.doi.org/10.1074/jbc.M202498200
- ↑ Davies SM, Rackham O, Shearwood AM, Hamilton KL, Narsai R, Whelan J, Filipovska A. Pentatricopeptide repeat domain protein 3 associates with the mitochondrial small ribosomal subunit and regulates translation. FEBS Lett. 2009 Jun 18;583(12):1853-8. Epub 2009 May 8. PMID:19427859 doi:http://dx.doi.org/S0014-5793(09)00357-3
- ↑ Khawaja A, Itoh Y, Remes C, Spahr H, Yukhnovets O, Hofig H, Amunts A, Rorbach J. Distinct pre-initiation steps in human mitochondrial translation. Nat Commun. 2020 Jun 10;11(1):2932. doi: 10.1038/s41467-020-16503-2. PMID:32522994 doi:http://dx.doi.org/10.1038/s41467-020-16503-2
