Department of Structural Biology, Weizmann Institute, 76100 Rehovot, Israel.
Angew Chem Int Ed Engl. 2010 Jun 14;49(26):4341-54. doi: 10.1002/anie.201001297.
High-resolution structures of ribosomes, the cellular machines that translate the genetic code into proteins, revealed the decoding mechanism, detected the mRNA path, identified the sites of the tRNA molecules in the ribosome, elucidated the position and the nature of the nascent proteins exit tunnel, illuminated the interactions of the ribosome with non-ribosomal factors, such as the initiation, release and recycling factors, and provided valuable information on ribosomal antibiotics, their binding sites, modes of action, principles of selectivity and the mechanisms leading to their resistance. Notably, these structures proved that the ribosome is a ribozyme whose active site, namely where the peptide bonds are being formed, is situated within a universal symmetrical region that is embedded in the otherwise asymmetric ribosome structure. As this symmetrical region is highly conserved and provides the machinery required for peptide bond formation and for ribosome polymerase activity, it may be the remnant of the proto-ribosome, a dimeric prebiotic machine that formed peptide bonds and non-coded polypeptide chains. Structures of complexes of ribosomes with antibiotics targeting them revealed the principles allowing for their clinical use, identified resistance mechanisms and showed the structural bases for discriminating pathogenic bacteria from hosts, hence providing valuable structural information for antibiotics improvement and for the design of novel compounds that can serve as antibiotics.
核糖体的高分辨率结构，即细胞内将遗传密码翻译成蛋白质的机器，揭示了解码机制，检测了 mRNA 路径，确定了 tRNA 分子在核糖体中的位置，阐明了新生蛋白质出口隧道的位置和性质，揭示了核糖体与非核糖体因子（如起始、释放和循环因子）的相互作用，并提供了关于核糖体抗生素的宝贵信息，包括它们的结合位点、作用模式、选择性原则以及导致其耐药性的机制。值得注意的是，这些结构证明核糖体是一种核酶，其活性位点，即肽键形成的部位，位于一个普遍的对称区域内，该区域嵌入在不对称的核糖体结构中。由于这个对称区域高度保守，提供了形成肽键和核糖体聚合酶活性所需的机制，它可能是原核核糖体的残余部分，原核核糖体是一种形成肽键和非编码多肽链的二聚前生物机器。核糖体与针对它们的抗生素的复合物结构揭示了允许其临床应用的原则，确定了耐药机制，并显示了区分病原菌和宿主的结构基础，从而为抗生素的改进和新型化合物的设计提供了有价值的结构信息，这些化合物可以作为抗生素。
