Department of Biology, Institute of Molecular Biology and Biophysics, Otto-Stern-Weg 5, ETH Zurich, CH-8093 Zurich, Switzerland.
Department of Biology, Institute of Molecular Systems Biology, Auguste-Piccard-Hof 1, ETH Zurich, CH-8093 Zurich, Switzerland.
Science. 2015 Apr 17;348(6232):303-8. doi: 10.1126/science.aaa3872. Epub 2015 Apr 2.
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.
哺乳动物线粒体核糖体(mitoribosomes)合成对线粒体功能至关重要的线粒体编码膜蛋白。在这里,我们通过冷冻电子显微镜和化学交联/质谱法以 3.8 埃的分辨率呈现了完整的猪 55S 线粒体核糖体的原子结构。通过聚焦对齐,解析了复合物中 28S 亚基的结构,分辨率为 3.6 埃,这使得构建包括其所有 15 个线粒体核糖体特异性蛋白在内的详细原子结构成为可能。该结构揭示了 55S 线粒体核糖体的亚基间接触、线粒体核糖体信使 RNA(mRNA)结合通道的分子结构及其与转移 RNA 的相互作用,并深入了解了 mRNA 招募到 28S 亚基的高度专业化机制。此外,该结构有助于理解氨基糖苷类耳毒性的机制。