Mrazek Jan, Toso Daniel, Ryazantsev Sergey, Zhang Xing, Zhou Z Hong, Fernandez Beatriz Campo, Kickhoefer Valerie A, Rome Leonard H
Department of Biological Chemistry, David Geffen School of Medicine, ‡Department of Microbiology, Immunology & Molecular Genetics, and §California Nanosystems Institute, University of California at Los Angeles , Los Angeles, California 90095, United States.
ACS Nano. 2014 Nov 25;8(11):11552-9. doi: 10.1021/nn504778h. Epub 2014 Oct 30.
Ribosomes are molecular machines that function in polyribosome complexes to translate genetic information, guide the synthesis of polypeptides, and modulate the folding of nascent proteins. Here, we report a surprising function for polyribosomes as a result of a systematic examination of the assembly of a large ribonucleoprotein complex, the vault particle. Structural and functional evidence points to a model of vault assembly whereby the polyribosome acts like a 3D nanoprinter to direct the ordered translation and assembly of the multi-subunit vault homopolymer, a process which we refer to as polyribosome templating. Structure-based mutagenesis and cell-free in vitro expression studies further demonstrated the critical importance of the polyribosome in vault assembly. Polyribosome templating prevents chaos by ensuring efficiency and order in the production of large homopolymeric protein structures in the crowded cellular environment and might explain the origin of many polyribosome-associated molecular assemblies inside the cell.
核糖体是在多核糖体复合物中发挥作用的分子机器，用于翻译遗传信息、指导多肽合成并调节新生蛋白质的折叠。在此，我们通过对一种大型核糖核蛋白复合物——穹窿体颗粒的组装进行系统研究，报告了多核糖体的一项惊人功能。结构和功能证据指向一种穹窿体组装模型，即多核糖体就像一台3D纳米打印机，指导多亚基穹窿体同聚物的有序翻译和组装，我们将这一过程称为多核糖体模板化。基于结构的诱变和无细胞体外表达研究进一步证明了多核糖体在穹窿体组装中的关键重要性。多核糖体模板化通过确保在拥挤的细胞环境中高效有序地产生大型同聚蛋白质结构，防止了混乱，并且可能解释了细胞内许多与多核糖体相关的分子组装体的起源。
