Cryo-EM structure of the small subunit of the mammalian mitochondrial ribosome

Area of Science:

• Cell Biology
• Structural Biology
• Biochemistry

Background:

• Mitochondrial ribosomes (mitoribosomes) synthesize essential proteins for oxidative phosphorylation.
• Mammalian mitoribosomes differ significantly from bacterial counterparts, featuring smaller rRNAs and numerous unique proteins.
• These unique proteins have extensions and insertions, suggesting a distinct evolutionary path.

Purpose of the Study:

• To present the cryo-electron microscopy (cryo-EM) structure of the mammalian mitoribosome's small subunit (SSU).
• To elucidate the role of mitochondrial-specific ribosomal proteins (MRPs) and their extensions in mitoribosome architecture.
• To understand how the mitoribosome structure facilitates the translation of mitochondrial-specific mRNAs.

Main Methods:

• Cryo-electron microscopy (cryo-EM) structure determination of the 28S small subunit (SSU) of the mammalian 55S mitoribosome.
• Analysis of mitochondrial ribosomal proteins (MRPs), including mito-specific extensions and additional proteins.
• Computational docking of the large subunit (LSU) coordinates into the 55S mitoribosome cryo-EM map.

Main Results:

• The mito-specific extensions in homologous MRPs are key for inter-MRP contacts and interactions with mito-specific MRPs.
• Most mito-specific MRPs and extensions are located peripherally but significantly line mRNA and tRNA paths.
• Mito-specific MRPs in both SSU and LSU are directly involved in forming six of the 15 intersubunit bridges.

Conclusions:

• The structure suggests a stepwise evolution of the mitoribosome architecture.
• The unique structural organization of the mito-SSU is tailored for recruiting mito-specific mRNAs, often lacking 5' leader sequences.
• Mito-specific proteins play a critical role in mitoribosome assembly and function, particularly in intersubunit interactions essential for translation.