Structure of Human Mitochondrial Translation Initiation Factor 3 Bound to the Small Ribosomal Subunit

• Published in: iScience 2019-02, Vol.12, p.76-86
• Main Authors: Koripella, Ravi K, Sharma, Manjuli R, Haque, Md Emdadul, Risteff, Paul, Spremulli, Linda L, Agrawal, Rajendra K
• Format: Article
• Language: English
• ISSN: 2589-0042; 2589-0042
• DOI: 10.1016/j.isci.2018.12.030

The human mitochondrial translational initiation factor 3 (IF3 ) 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 IF3 . Unique contacts observed between the 28S subunit and N-terminal domain of IF3 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 IF3 in mitochondrial translation initiation.