美国哈佛医学院Philip J. Kranzusch课题组揭示Gabija抗噬菌体防御和病毒免疫逃避的结构基础。相关论文于2023年11月22日在线发表于《自然》期刊。
研究人员利用X射线晶体学和冷冻电镜确定了Gabija蛋白如何组装成约500 kDa的超分子复合物来降解噬菌体DNA。Gabija蛋白A(GajA)是一种DNA内切酶,可四聚体化形成抗噬菌体防御复合物的核心。两组Gabija蛋白B(GajB)二聚体对接在复合物的两侧,形成4:4 GajAB组合,这对体内的噬菌体抗性至关重要。这些研究表明,噬菌体编码的蛋白Gabija抗防御 1(Gad1)可直接与Gabija GajAB复合物结合并使防御失活。病毒抑制状态的冷冻电镜结构显示,Gad1形成了一个八聚体网,包裹着GajAB复合物并抑制DNA的识别和切割。这些研究结果揭示了Gabija抗噬菌体防御复合物组装的结构基础,并定义了一种独特的病毒免疫逃避机制。
研究人员表示,细菌编码了数百种不同的防御系统,可防止病毒感染并抑制噬菌体繁殖。Gabija是最普遍的抗噬菌体防御系统之一,在所有已测序的细菌和古细菌基因组中出现率超过15%,但人们对Gabija如何保护细胞免受病毒感染的分子基础仍然知之甚少。
附:英文原文
Title: Structural basis of Gabija anti-phage defence and viral immune evasion
Author: Antine, Sadie P., Johnson, Alex G., Mooney, Sarah E., Leavitt, Azita, Mayer, Megan L., Yirmiya, Erez, Amitai, Gil, Sorek, Rotem, Kranzusch, Philip J.
Issue&Volume: 2023-11-22
Abstract: Bacteria encode hundreds of diverse defense systems that protect from viral infection and inhibit phage propagation1–5. Gabija is one of the most prevalent anti-phage defense systems, occurring in >15% of all sequenced bacterial and archaeal genomes1,6,7, but the molecular basis of how Gabija defends cells from viral infection remains poorly understood. Here we use X-ray crystallography and cryo-EM to define how Gabija proteins assemble into an ~500 kDa supramolecular complex that degrades phage DNA. Gabija protein A (GajA) is a DNA endonuclease that tetramerizes to form the core of the anti-phage defense complex. Two sets of Gabija protein B (GajB) dimers dock at opposite sides of the complex and create a 4:4 GajAB assembly that is essential for phage resistance in vivo. We show that a phage-encoded protein Gabija anti-defense 1 (Gad1) directly binds the Gabija GajAB complex and inactivates defense. A cryo-EM structure of the virally inhibited state reveals that Gad1 forms an octameric web that encases the GajAB complex and inhibits DNA recognition and cleavage. Our results reveal the structural basis of assembly of the Gabija anti-phage defense complex and define a unique mechanism of viral immune evasion.
DOI: 10.1038/s41586-023-06855-2
Source: https://www.nature.com/articles/s41586-023-06855-2
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/
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