9OJM

Human mitochondrial 28S PIC with tRNA and mtIF2

Summary for 9OJM

• Entry DOI: 10.2210/pdb9ojm/pdb
• EMDB information: 70533 70544
• Descriptor: Small ribosomal subunit protein mS34, Small ribosomal subunit protein uS2m, 28S ribosomal protein S24, mitochondrial, ... (42 entities in total)
• Functional Keywords: mitochondrial ribosome 28s pre-initiation complex, ribosome
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 34
• Total formula weight: 1069940.60

Authors

Kober, D.L.,Wang, J. (deposition date: 2025-05-08, release date: 2026-03-18, Last modification date: 2026-04-22)

Primary citation

Shen, S.,Xu, Y.,Kober, D.L.,Wang, J.
Mechanisms of human mitochondrial leaderless mRNA translation initiation.
Nat Commun, 2026

PubMed Abstract: Mitochondrial translation is essential for cellular function, and its dysregulation is associated with mitochondrial disorders and cancer. However, the mechanisms by which human mitochondrial ribosomes initiate translation remain poorly understood, particularly because mitochondrial mRNAs generally lack the 5' untranslated regions that guide translation initiation in bacterial and cytoplasmic systems. Using real-time single-molecule fluorescence measurements, biochemical assays, and cryo-EM analysis, we show that human mitochondrial translation initiation occurs through two parallel pathways. In one pathway, leaderless mRNA first loads onto the 28S small subunit, followed by recruitment of the 39S large subunit to form the 55S initiation complex. In the second pathway, a preassembled 55S monosome directly loads onto leaderless mRNA. Both pathways require recruitment of mtIF2 and fMet-tRNA before mRNA binding. However, the monosome-loading pathway tolerates non-formylated Met-tRNA and is suppressed by mtIF3. Together, these findings define the heterogeneous pathways of human mitochondrial translation initiation on leaderless mRNAs.

PubMed: 41935065
DOI: 10.1038/s41467-026-71535-4

Experimental method

ELECTRON MICROSCOPY (2.5 Å)