Structural studies on factor assisted protein folding and targeting

在每个生物体中，遗传密码到功能蛋白质的翻译都是在核糖体上进行的，核糖体是一种含有超过2.3个丙二醛的大分子机器。由于核糖体在细胞活力中起着中心作用，它们的活性受到一系列辅助因子的强烈调控，是天然抗生素的主要靶点。在过去的几年里，小的(30S)和大的(50S)核糖体亚基的高分辨率结构彻底改变了我们对核糖体结构和功能的理解。在我们团队中，我们处于能够制备四种不同类型的核糖体晶体的独特位置：嗜热嗜热杆菌30S和50S亚基、耐辐射变形球菌和嗜热嗜热杆菌70S核糖体。这项建议的目的是利用我们实验室生产的核糖体和核糖体晶体作为制备和研究新型核糖体复合体的平台。我们的目标包括获得核糖体在各种功能状态下的高分辨率结构：(I)转位前和转位后的结构，(Ii)多肽前键的形成，以及(Iii)与各种翻译和调节因子的复合体。我们预测，所获得的结果将增加我们对翻译过程的理解，并将对合理开发新的抗生素具有潜在的用途。

In every organism, translation of the genetic code into functional proteins is performed on the ribosome, a macromolecular machine of more than 2.3 MDa. Since ribosomes play a central cole in cell viability, their activity is intensely regulated by a host of ancillary factors and represent a major target of natural antibiotics. The high-resolution structures of the small (30S) and large (50S) ribosome subunit, in the past few years have revolutionized our understanding of ribosome structure and function. In our group we are in the unique position of being able to prepare four different types of ribosome crystals: Thermus thermophilus 30S and 50S subunits, Deinococcus radiodurans and T. thermophilus 70S ribosome. The aim of this proposal is to utilise the ribosomes and ribosome crystals produced in our laboratory as a platform for the preparation and study of novel ribosomal complexes. Our goals include obtaining high-resolution structures of the ribosome in various functional states: (i) both pre- and post-translocation, (ii) pre-peptide bond formation, as well as (iii) in complex with various translational and regulatory factors. We predict that the results that will be obtained will increase our comprehension of the translational process and will be of potential use for the rational development of new antibiotics.