美国耶鲁医学院David G. Schatz研究团队发现剪切-粘贴转座过程中RAG样转座酶的结构。2019年11月13日，《自然》在线发表了这一成果。
课题组报道了Transib（一种来自棉铃虫的RAG1样转座酶）的晶体结构和五种冷冻电镜结构。他们捕获了从apo酶到末端链转移复合物的整个转座过程，其中转座子末端共价结合到靶标上DNA，分辨率为3.0–4.6Å。这些结构揭示了一个蝴蝶状的复合物，该复合物经历了两个周期的显著构象变化，其中转座酶的“翅膀”张开以结合底物DNA，进而对其进行切割，然后张开以释放侧翼DNA，再次闭合以捕获和攻击靶标DNA。Transib具有独特的结构元件，可弥补RAG2伴侣的缺失，包括与转座靶位点相互作用的环和拉长和收缩的手风琴状C末端尾巴，以帮助控制酶的开放和闭合以及活性位点的组装。他们的结果揭示了真核切割并粘贴式转座酶的详细反应途径，并阐明了RAG重组酶进化的最早步骤。
据介绍，转座子在基因组进化过程中具有举足轻重的作用，并被认为是RAG1-RAG2重组酶2的进化先祖，RAG1-RAG2重组酶2是颌骨脊椎动物适应性免疫系统的重要组成部分。
附：英文原文
Title: Structures of a RAG-like transposase during cut-and-paste transposition
Author: Chang Liu, Yang Yang, David G. Schatz
Issue&Volume: 2019-11-13
Abstract: Transposons have had a pivotal role in genome evolution1 and are believed to be the evolutionary progenitors of the RAG1RAG2 recombinase2, an essential component of the adaptive immune system in jawed vertebrates3. Here we report one crystal structure and five cryo-electron microscopy structures of Transib4,5, a RAG1-like transposase from Helicoverpa zea, that capture the entire transposition process from the apo enzyme to the terminal strand transfer complex with transposon ends covalently joined to target DNA, at resolutions of 3.04.6 . These structures reveal a butterfly-shaped complex that undergoes two cycles of marked conformational changes in which the wings of the transposase unfurl to bind substrate DNA, close to execute cleavage, open to release the flanking DNA and close again to capture and attack target DNA. Transib possesses unique structural elements that compensate for the absence of a RAG2 partner, including a loop that interacts with the transposition target site and an accordion-like C-terminal tail that elongates and contracts to help to control the opening and closing of the enzyme and assembly of the active site. Our findings reveal the detailed reaction pathway of a eukaryotic cut-and-paste transposase and illuminate some of the earliest steps in the evolution of the RAG recombinase. Analysis of multiple structures of the Helicoverpa zea DNA transposase Transib, determined by X-ray crystallography and cryo-electron microscopy, reveals the detailed pathway of the transposition reaction and sheds light on the evolution of the RAG recombinase.
DOI: 10.1038/s41586-019-1753-7
Source:https://www.nature.com/articles/s41586-019-1753-7
Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
官方网址：http://www.nature.com/
投稿链接：http://www.nature.com/authors/submit_manuscript.html
本期文章：《自然》：Online/在线发表
