Science for Life Laboratory, Department of Biochemistry and Biophysics, Stockholm University, 17165, Solna, Sweden.
Department of Medical Biochemistry and Biophysics, Karolinska Institutet, 17165, Solna, Sweden.
Nat Commun. 2020 Oct 14;11(1):5187. doi: 10.1038/s41467-020-18830-w.
Mitoribosomes are specialized protein synthesis machineries in mitochondria. However, how mRNA binds to its dedicated channel, and tRNA moves as the mitoribosomal subunit rotate with respect to each other is not understood. We report models of the translating fungal mitoribosome with mRNA, tRNA and nascent polypeptide, as well as an assembly intermediate. Nicotinamide adenine dinucleotide (NAD) is found in the central protuberance of the large subunit, and the ATPase inhibitory factor 1 (IF) in the small subunit. The models of the active mitoribosome explain how mRNA binds through a dedicated protein platform on the small subunit, tRNA is translocated with the help of the protein mL108, bridging it with L1 stalk on the large subunit, and nascent polypeptide paths through a newly shaped exit tunnel involving a series of structural rearrangements. An assembly intermediate is modeled with the maturation factor Atp25, providing insight into the biogenesis of the mitoribosomal large subunit and translation regulation.
线粒体核糖体是线粒体中专门的蛋白质合成机器。然而,mRNA 如何与其专用通道结合,以及 tRNA 在核糖体亚基相对于彼此旋转时如何移动,目前尚不清楚。我们报告了翻译真菌线粒体核糖体的模型,其中包括 mRNA、tRNA 和新生多肽,以及一个组装中间体。烟酰胺腺嘌呤二核苷酸(NAD)存在于大亚基的中央突起中,而 ATP 酶抑制因子 1(IF)存在于小亚基中。活性线粒体核糖体的模型解释了 mRNA 如何通过小亚基上的专用蛋白平台结合,tRNA 在蛋白 mL108 的帮助下移位,与大亚基上的 L1 茎连接,并通过新形成的出口隧道引导新生多肽穿过一系列结构重排。使用成熟因子 Atp25 构建了一个组装中间体模型,为线粒体核糖体大亚基的生物发生和翻译调控提供了深入了解。