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一种crAss样噬菌体病毒RNAP的结构和功能
2020-11-20 14:18

俄罗斯斯科尔科沃科技学院Maria L. Sokolova、Konstantin V. Severinov以及美国德克萨斯大学医学分校Petr G. Leiman课题组合作取得最新进展。他们揭示老人一种crAss样噬菌体病毒RNA聚合酶(RNAPs)的结构和功能。这一研究成果发表在2020年11月18日出版的《自然》杂志上。

使用波氏纤维藻crAss样噬菌体phi14:2作为模型系统,他们表明该蛋白是一种DNA依赖性RNAP,与噬菌体DNA一起转移到宿主细胞中并转录早期噬菌体基因。他们确定了这种2180残基酶的自抑制状态的晶体结构,该结构可能发生在病毒体包装之前。这种构象是通过与活动位点相互作用并占据RNA-DNA杂化物结合的空腔的裂隙,来阻滞结构域占据。

从结构上讲,尽管大多数phi14:2 RNAP结构(将近1600个残基)都映射到蛋白质折叠空间的新区域,phi14:2 RNAP最类似于参与RNA干扰的真核RNAP。考虑到这种结构上的相似性,他们表明真核RNA干扰聚合酶起源于噬菌体,与线粒体转录装置同时出现。

研究人员表示,CrAss样噬菌体是最近描述的一种广泛的病毒,其中包括人类肠道中最丰富的病毒。所有crAss样噬菌体的基因组都编码一个大的病毒体包装蛋白,该蛋白含有DFDxD序列基序,该基序在细胞多亚基RNAP中形成催化位点。

附:英文原文

Title: Structure and function of virion RNA polymerase of a crAss-like phage

Author: Arina V. Drobysheva, Sofia A. Panafidina, Matvei V. Kolesnik, Evgeny I. Klimuk, Leonid Minakhin, Maria V. Yakunina, Sergei Borukhov, Emelie Nilsson, Karin Holmfeldt, Natalya Yutin, Kira S. Makarova, Eugene V. Koonin, Konstantin V. Severinov, Petr G. Leiman, Maria L. Sokolova

Issue&Volume: 2020-11-18

Abstract: CrAss-like phages are a recently described expansive group of viruses that includes the most abundant virus in the human gut1,2,3. The genomes of all crAss-like phages encode a large virion-packaged protein2,4 that contains a DFDxD sequence motif, which forms the catalytic site in cellular multisubunit RNA polymerases (RNAPs)5. Here, using Cellulophaga baltica crAss-like phage phi14:2 as a model system, we show that this protein is a DNA-dependent RNAP that is translocated into the host cell along with the phage DNA and transcribes early phage genes. We determined the crystal structure of this 2,180-residue enzyme in a self-inhibited state, which probably occurs before virion packaging. This conformation is attained with the help of a cleft-blocking domain that interacts with the active site and occupies the cavity in which the RNA–DNA hybrid binds. Structurally, phi14:2 RNAP is most similar to eukaryotic RNAPs that are involved in RNA interference6,7, although most of the phi14:2 RNAP structure (nearly 1,600 residues) maps to a new region of the protein fold space. Considering this structural similarity, we propose that eukaryal RNA interference polymerases have their origins in phage, which parallels the emergence of the mitochondrial transcription apparatus8.

DOI: 10.1038/s41586-020-2921-5

Source: https://www.nature.com/articles/s41586-020-2921-5

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

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