The complete structure of the 55S mammalian mitochondrial ribosome

Resolving whole mitoribosomes Mitochondria probably evolved from a prokaryotic cell living within a proto-eukaryotic cell. Consequently, mitochondria have lost much of their genomic DNA, except for a few genes that require highly divergent mitoribosomes for protein translation. Greber et al. and Amunts et al. have used cryo–electron microscopy to uncover the structure of this complex (see the Perspective by Beckmann and Hermann) and reveal an unusual mRNA binding channel. The structure supplies clues for how aminoglycoside antibiotics might inhibit mitoribosomes and how mutations in mitoribosomes might cause human disease. Science, this issue p. 303, p. 288; see also A. Amunts et al., Science, 3 April, p. 95 The protein-synthesizing machinery of mammalian mitochondria differs substantially from bacterial and eukaryotic ribosomes. [Also see Perspective by Beckmann and Hermann] Mammalian mitochondrial ribosomes (mitoribosomes) synthesize mitochondrially encoded membrane proteins that are critical for mitochondrial function. Here we present the complete atomic structure of the porcine 55S mitoribosome at 3.8 angstrom resolution by cryo–electron microscopy and chemical cross-linking/mass spectrometry. The structure of the 28S subunit in the complex was resolved at 3.6 angstrom resolution by focused alignment, which allowed building of a detailed atomic structure including all of its 15 mitoribosomal-specific proteins. The structure reveals the intersubunit contacts in the 55S mitoribosome, the molecular architecture of the mitoribosomal messenger RNA (mRNA) binding channel and its interaction with transfer RNAs, and provides insight into the highly specialized mechanism of mRNA recruitment to the 28S subunit. Furthermore, the structure contributes to a mechanistic understanding of aminoglycoside ototoxicity.

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