蛋白合成的終止在細(xì)菌中能以很高的保真性實(shí)現(xiàn),，這個(gè)時(shí)候mRNA上的“終止密碼子”與釋放因子RF1 和 RF2結(jié)合，而不是與另一種帶有一個(gè)氨基酸的tRNA相結(jié)合,，同時(shí)一個(gè)新合成的蛋白被釋放出來,。生物谷啟用新域名 www.bioon.net
隨著最近幾種終止復(fù)合物的晶體結(jié)構(gòu)的發(fā)表，現(xiàn)在有可能對“終止密碼子”能量狀態(tài)的讀出結(jié)果進(jìn)行計(jì)算分析,，同時(shí)搞清釋放因子結(jié)合的這種高準(zhǔn)確性的起源,。
對14種不同終止復(fù)合物進(jìn)行的分子動態(tài)模擬顯示，“終止密碼子”的讀出結(jié)果取決于幾個(gè)以前沒有被識別出的互動和識別開關(guān),，這些開關(guān)不能用三肽反密碼子“tRNA mimicry”模型來描述,。(生物谷Bioon.net)
生物谷推薦原文出處：
Nature doi:10.1038/nature09082
Principles of stop-codon reading on the ribosome
Johan Sund, Martin Andér & Johan ?qvist
In termination of protein synthesis, the bacterial release factors RF1 and RF2 bind to the ribosome through specific recognition of messenger RNA stop codons and trigger hydrolysis of the bond between the nascent polypeptide and the transfer RNA at the peptidyl-tRNA site, thereby releasing the newly synthesized protein. The release factors are highly specific for a U in the first stop-codon position1 and recognize different combinations of purines in the second and third positions, with RF1 reading UAA and UAG and RF2 reading UAA and UGA. With recently determined crystal structures of termination complexes2, 3, 4, it has become possible to decipher the energetics of stop-codon reading by computational analysis and to clarify the origin of the high release-factor binding accuracy. Here we report molecular dynamics free-energy calculations on different cognate and non-cognate termination complexes. The simulations quantitatively explain the basic principles of decoding in all three codon positions and reveal the key elements responsible for specificity of the release factors. The overall reading mechanism involves hitherto unidentified interactions and recognition switches that cannot be described in terms of a tripeptide anticodon model. Further simulations of complexes with tRNATrp, the tRNA recognizing the triplet codon for Trp, explain the observation of a ‘leaky’ stop codon5 and highlight the fundamentally different third position reading by RF2, which leads to a high stop-codon specificity with strong discrimination against the Trp codon. The simulations clearly illustrate the versatility of codon reading by protein, which goes far beyond tRNA mimicry.
