Structure of Human Mitochondrial Translation Initiation Factor 3 Bound to the Small Ribosomal Subunit
| Autor: | Rajendra K. Agrawal, Paul Risteff, Manjuli R. Sharma, Ravi Kiran Koripella, Linda L. Spremulli, Md. Emdadul Haque |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
chemistry.chemical_classification Messenger RNA Multidisciplinary Protein subunit 02 engineering and technology Biological Sciences 021001 nanoscience & nanotechnology Protein Structure Aspects Article 3. Good health Cell biology Amino acid 03 medical and health sciences 030104 developmental biology Eukaryotic translation Structural biology chemistry Structural Biology Ribosomal protein Transfer RNA lcsh:Q CTD lcsh:Science 0210 nano-technology |
| Zdroj: | iScience iScience, Vol 12, Iss, Pp 76-86 (2019) |
| ISSN: | 2589-0042 |
| DOI: | 10.1016/j.isci.2018.12.030 |
| Popis: | Summary The human mitochondrial translational initiation factor 3 (IF3mt) carries mitochondrial-specific amino acid extensions at both its N and C termini (N- and C-terminal extensions [NTE and CTE, respectively]), when compared with its eubacterial counterpart. Here we present 3.3- to 3.5-Å-resolution cryoelectron microscopic structures of the mammalian 28S mitoribosomal subunit in complex with human IF3mt. Unique contacts observed between the 28S subunit and N-terminal domain of IF3mt explain its unusually high affinity for the 28S subunit, whereas the position of the mito-specific NTE suggests NTE's role in binding of initiator tRNA to the 28S subunit. The location of the C-terminal domain (CTD) clarifies its anti-association activity, whereas the orientation of the mito-specific CTE provides a mechanistic explanation for its role in destabilizing initiator tRNA in the absence of mRNA. Furthermore, our structure hints at a possible role of the CTD in recruiting leaderless mRNAs for translation initiation. Our findings highlight unique features of IF3mt in mitochondrial translation initiation. Graphical Abstract Highlights • High-resolution cryo-EM study of the mammalian 28S mitoribosome-IF3mt complex • Interaction between the 28S and IF3mt's NTD explains NTD's unusual high affinity • Provides insights into role of IF3mt's N-terminal extension in initiator tRNA binding • Provides insights into roles of IF3mt's CTD and C-terminal extension in mRNA sensing Biological Sciences; Structural Biology; Protein Structure Aspects |
| Databáze: | OpenAIRE |
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