在蛋白合成期間,，核糖體在解碼中心依照信使RNA (mRNA)上的三聯(lián)體密碼精確的選擇轉(zhuǎn)移RNA (tRNAs)。tRNA的選擇開(kāi)始于延伸因子Tu,，它可以傳遞tRNA到氨酰tRNA結(jié)合位點(diǎn)即A位點(diǎn),，還可以在解碼中心水解GTP來(lái)建立密碼子-反密碼子之間的相互作用。在隨后的校對(duì)階段,，核糖體重新檢查tRNA,，如果被發(fā)現(xiàn)不能正確配對(duì)于A位點(diǎn)該tRNA便會(huì)被排除。過(guò)去一直認(rèn)為,，16S核糖體RNA普遍保守的G53,、A1492和 A1493對(duì)tRNA結(jié)合在A位點(diǎn)至關(guān)重要，它們可以積極的監(jiān)視同源性tRNA ,，這種對(duì)正確配對(duì)的識(shí)別會(huì)引起核糖體整體構(gòu)象的改變（即結(jié)構(gòu)域閉合）,。近日，法國(guó)斯特拉斯堡大學(xué)的Gulnara Yusupova等人研究發(fā)現(xiàn)了新的核糖體解碼機(jī)制,，相關(guān)研究發(fā)表在《自然》（Nature）上,。
實(shí)驗(yàn)過(guò)程中，通過(guò)在校對(duì)階段模擬同源的或者是近同源狀態(tài)的編碼中心,，基于在3.1-3.4A分辨率下70S核糖體的六個(gè)X光結(jié)構(gòu),，研究人員提出了一個(gè)完整的解碼機(jī)制。研究表明：在結(jié)合同源的或者是近同源的tRNA時(shí),，30S亞基遭受了同樣的結(jié)構(gòu)域閉合,。30S亞基的構(gòu)象改變形成了一個(gè)解碼中心，驅(qū)使mRNA A密碼子的前兩個(gè)核苷酸必須以Watson-Crick堿基配對(duì)方式嚴(yán)格配對(duì),。
當(dāng)U·G和G·U錯(cuò)配時(shí),，一般被認(rèn)為會(huì)形成不穩(wěn)定的堿基對(duì)，在第一個(gè)或者是第二個(gè)密碼子-反密碼子位置,，解碼中心會(huì)迫使該配對(duì)通過(guò)幾何變化接近于正確的C·G配對(duì)形式,。這本身或者在密碼子-反密碼子的小螺旋及反密碼子環(huán)存在扭曲，導(dǎo)致近同源的tRNA從核糖體離開(kāi),。（生物谷Deepblue編譯）
doi: 10.1038/nature10913
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A new understanding of the decoding principle on the ribosome
>Natalia Demeshkina, Lasse Jenner, Eric Westhof, Marat Yusupov & Gulnara Yusupoval.
During protein synthesis, the ribosome accurately selects transfer RNAs (tRNAs) in accordance with the messenger RNA (mRNA) triplet in the decoding centre. tRNA selection is initiated by elongation factor Tu, which delivers tRNA to the aminoacyl tRNA-binding site (A site) and hydrolyses GTP upon establishing codon–anticodon interactions in the decoding centre.At the following proofreading step the ribosome re-examines the tRNA and rejects it if it does not match the A codon. It was suggested that universally conserved G530, A1492 and A1493 of 16S ribosomal RNA, critical for tRNA binding in the A site, actively monitor cognate tRNA, and that recognition of the correct codon–anticodon duplex induces an overall ribosome conformational change (domain closure). Here we propose an integrated mechanism for decoding based on six X-ray structures of the 70S ribosome determined at 3.1–3.4A resolution, modelling cognate or near-cognate states of the decoding centre at the proofreading step. We show that the 30S subunit undergoes an identical domain closure upon binding of either cognate or near-cognate tRNA. This conformational change of the 30S subunit forms a decoding centre that constrains the mRNA in such a way that the first two nucleotides of the A codon are limited to form Watson–Crick base pairs.When U·G and G·U mismatches, generally considered to form wobble base pairs, are at the first or second codon–anticodon position, the decoding centre forces this pair to adopt the geometry close to that of a canonical C·G pair.This by itself, or with distortions in the codon–anticodon mini-helix and the anticodon loop, causes the near-cognate tRNA to dissociate from the ribosome.
