THE ALLOSTERIC 3-SITE MODEL FOR THE RIBOSOMAL ELONGATION CYCLE - FEATURES AND FUTURE
THE ALLOSTERIC 3-SITE MODEL FOR THE RIBOSOMAL ELONGATION CYCLE - FEATURES AND FUTURE
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DOI：
10.1021/bi00473a001
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发表时间：
1990-05-29
期刊：
影响因子：
2.9
通讯作者：
NIERHAUS, KH
中科院分区：
文献类型：
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作者：
NIERHAUS, KH
克努德湾Nierhaus Max-Planck-Institut fur Molekulare Genetik，Abteilung Wittmann，Ihnestrasse 73，D-1000 Berlin-Dahlem，West德国1989年10月25日接收; 1990年1月4日接收的修订版手册摘要：核糖体包含三个tRNA结合位点，即，氨酰-tRNA的A位点（解码位点）、肽酰-tRNA的P位点和脱酰化tRNA的E位点（E代表出口）。在负协同性意义上，E和A位点之间的变构连接的惊人发现有三个结果：（a）它改善了氨酰-tRNA的正确选择，同时防止了非同源氨酰-tRNA在解码过程中的干扰;（B）它为核糖体的精确性提供了一种解释，而不必求助于校对假说;（c）它加深了我们对某些抗生素作用方式的理解。在20世纪60年代早期，沃森（1963，1964）和李普曼（1963）提出了一个这种延伸循环的模型，其中核糖体含有两个tRNA结合位点，即肽酰tRNA的P位点和新选择的氨酰tRNA的A位点。图1A展示了在双位点模型的框架中伸长循环的三个基本反应。核糖体的左半部分代表P位点，右半部分代表A位点。在反应1中，A位点被与该位点暴露的密码子同源的氨酰-tRNA占据。接下来，肽基转移酶，一种与核糖体大亚基相关的活性，从肽基-tRNA上切下肽基残基，并将其转移到A位点的氨酰-tRNA上（反应2）。结果是肽基-tRNA（延长了一个氨基酸）现在位于A位点，脱酰化的tRNA位于相邻的P位点。反应3是易位步骤，其中脱酰化的tRNA离开核糖体，肽基-tRNA从A位点移动到P位点，并且新的密码子侵入A位点。根据双位点模型，易位必然与脱酰tRNA的释放偶联。作为双位点模型的推论，易位后的核糖体总是包含一个tRNA，而易位前的核糖体包含两个tRNA。
Knud H. Nierhaus Max-Planck-Institut fur Molekulare Genetik, Abteilung Wittmann, Ihnestrasse 73, D-1000 Berlin-Dahlem, West Germany Received October 25, 1989; Revised Manuscript Received January 4, 1990 abstract: The ribosome contains three binding sites for tRNA, viz., the A site for aminoacyl-tRNA (decoding site), the P site forpeptidyl-tRNA, and the E site for deacylated tRNA (E for exit). The surprising finding of an allosteric linkage between the E and A sites in the sense of a negative cooperativity has three consequences:(a) it improves the proper selection of aminoacyl-tRNAs while preventing interference from noncognate aminoacyl-tRNAs in the decoding process,(b) it provides an explanation for the ribosomal accuracy without having to resort to the proofreading hypothesis, and (c) it has deepened our understanding of the mode of action of some antibiotics.The elongation cycle of the ribosome is a series of reactions in which the growing peptidyl chain is lengthened by one amino acid. In the early 1960s Watson (1963, 1964) and Lipmann (1963) suggested a model for this elongation cycle in which the ribosome contained two binding sites for tRNA, namely, the P site for the peptidyl-tRNA and the A site for the newly selected aminoacyl-tRNA. Figure 1A demonstrates the three basic reactions of the elongation cycle in the frame of the two-site model. The left half of the ribosome represents the P site andthe right half the A site. In reaction 1 the A site is occupied with an aminoacyl-tRNA cognate to the codon exposed at this site. Next, the peptidyltransferase, an activity associated with the large ribosomal subunit, cleaves off the peptidyl residue from the peptidyl-tRNA and transfers it to the aminoacyl-tRNA at the A site (reaction 2). The result is that the peptidyl-tRNA (extended by one amino acid) is now located at the A site and the deacylated tRNA is at the adjacent P site. Reaction 3 is the translocation step in which the deacylated tRNA leaves the ribosome, the peptidyl-tRNA moves from the A to the P site, and a new codon invades the A site. According to the two-site model, the translocation is necessarily coupled to the release of deacylated tRNA. As a corollary of the two-site model, the posttranslocational ribosome always contains one tRNA, whereas the pretranslocational ribosome contains two tRNAs.