Structural highlights
Function
[EIF2D_HUMAN] Translation initiation factor that is able to deliver tRNA to the P-site of the eukaryotic ribosome in a GTP-independent manner. The binding of Met-tRNA(I) occurs after the AUG codon finds its position in the P-site of 40S ribosomes, the situation that takes place during initiation complex formation on some specific RNAs. Its activity in tRNA binding with 40S subunits does not require the presence of the aminoacyl moiety. Possesses the unique ability to deliver non-Met (elongator) tRNAs into the P-site of the 40S subunit. In addition to its role in initiation, can promote release of deacylated tRNA and mRNA from recycled 40S subunits following ABCE1-mediated dissociation of post-termination ribosomal complexes into subunits.[1] [2]
Publication Abstract from PubMed
After having translated short upstream open reading frames, ribosomes can re-initiate translation on the same mRNA. This process, referred to as re-initiation, controls the translation of a large fraction of mammalian cellular mRNAs, many of which are important in cancer. Key ribosomal binding proteins involved in re-initiation are the eukaryotic translation initiation factor 2D (eIF2D) or the homologous complex of MCT-1/DENR. We determined the structures of these factors bound to the human 40S ribosomal subunit in complex with initiator tRNA positioned on an mRNA start codon in the P-site using a combination of cryoelectron microscopy and X-ray crystallography. The structures, supported by biochemical experiments, reveal how eIF2D emulates the function of several canonical translation initiation factors by using three independent, flexibly connected RNA binding domains to simultaneously monitor codon-anticodon interactions in the ribosomal P-site and position the initiator tRNA.
Structural and Functional Insights into Human Re-initiation Complexes.,Weisser M, Schafer T, Leibundgut M, Bohringer D, Aylett CHS, Ban N Mol Cell. 2017 Aug 3;67(3):447-456.e7. doi: 10.1016/j.molcel.2017.06.032. Epub, 2017 Jul 18. PMID:28732596[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Dmitriev SE, Terenin IM, Andreev DE, Ivanov PA, Dunaevsky JE, Merrick WC, Shatsky IN. GTP-independent tRNA delivery to the ribosomal P-site by a novel eukaryotic translation factor. J Biol Chem. 2010 Aug 27;285(35):26779-87. doi: 10.1074/jbc.M110.119693. Epub, 2010 Jun 21. PMID:20566627 doi:http://dx.doi.org/10.1074/jbc.M110.119693
- ↑ Skabkin MA, Skabkina OV, Dhote V, Komar AA, Hellen CU, Pestova TV. Activities of Ligatin and MCT-1/DENR in eukaryotic translation initiation and ribosomal recycling. Genes Dev. 2010 Aug 15;24(16):1787-801. doi: 10.1101/gad.1957510. PMID:20713520 doi:http://dx.doi.org/10.1101/gad.1957510
- ↑ Weisser M, Schafer T, Leibundgut M, Bohringer D, Aylett CHS, Ban N. Structural and Functional Insights into Human Re-initiation Complexes. Mol Cell. 2017 Aug 3;67(3):447-456.e7. doi: 10.1016/j.molcel.2017.06.032. Epub, 2017 Jul 18. PMID:28732596 doi:http://dx.doi.org/10.1016/j.molcel.2017.06.032
