Structural insight into arenavirus replication machinery

doi:10.1038/s41586-020-2114-2

GSTDTAP > 地球科学

DOI	10.1038/s41586-020-2114-2
	Structural insight into arenavirus replication machinery
	Zhang, Xiaheng 1; Smith, Russell T.1; Le, Chip 1; McCarver, Stefan J.2; Shireman, Brock T.2; Carruthers, Nicholas I.2; MacMillan, David W. C.1
	2020-02-17
发表期刊	NATURE
ISSN	0028-0836
EISSN	1476-4687
出版年	2020
卷号	579 期号:7800 页码:615-+
文章类型	Article
语种	英语
国家	Peoples R China
英文关键词	The authors provide high-resolution structures of two arenavirus polymerases, revealing that the active site of arenavirus polymerase is inherently switched on, without the requirement for allosteric activation by 5 ' -viral RNA, and that dimerization facilitates polymerase activity. Arenaviruses can cause severe haemorrhagic fever and neurological diseases in humans and other animals, exemplified by Lassa mammarenavirus, Machupo mammarenavirus and lymphocytic choriomeningitis virus, posing great threats to public health(1-4). These viruses encode a large multi-domain RNA-dependent RNA polymerase for transcription and replication of the viral genome(5). Viral polymerases are one of the leading antiviral therapeutic targets. However, the structure of arenavirus polymerase is not yet known. Here we report the near-atomic resolution structures of Lassa and Machupo virus polymerases in both apo and promoter-bound forms. These structures display a similar overall architecture to influenza virus and bunyavirus polymerases but possess unique local features, including an arenavirus-specific insertion domain that regulates the polymerase activity. Notably, the ordered active site of arenavirus polymerase is inherently switched on, without the requirement for allosteric activation by 5 ' -viral RNA, which is a necessity for both influenza virus and bunyavirus polymerases(6,7). Moreover, dimerization could facilitate the polymerase activity. These findings advance our understanding of the mechanism of arenavirus replication and provide an important basis for developing antiviral therapeutics.
领域	地球科学 ; 气候变化 ; 资源环境
收录类别	SCI-E
WOS记录号	WOS:000520406700004
WOS关键词	LYMPHOCYTIC CHORIOMENINGITIS ; L PROTEIN ; NONTEMPLATED BASES ; POLYMERASE ; VIRUS ; TERMINUS ; SYSTEM ; DOMAIN ; RNAS
WOS类目	Multidisciplinary Sciences
WOS研究方向	Science & Technology - Other Topics
引用统计
文献类型	期刊论文
条目标识符	http://119.78.100.173/C666/handle/2XK7JSWQ/281046
专题	地球科学资源环境科学气候变化
作者单位	1.Princeton Univ, Merck Ctr Catalysis, Princeton, NJ 08544 USA; 2.Janssen Res & Dev, San Diego, CA USA
推荐引用方式 GB/T 7714	Zhang, Xiaheng,Smith, Russell T.,Le, Chip,et al. Structural insight into arenavirus replication machinery[J]. NATURE,2020,579(7800):615-+.
APA	Zhang, Xiaheng.,Smith, Russell T..,Le, Chip.,McCarver, Stefan J..,Shireman, Brock T..,...&MacMillan, David W. C..(2020).Structural insight into arenavirus replication machinery.NATURE,579(7800),615-+.
MLA	Zhang, Xiaheng,et al."Structural insight into arenavirus replication machinery".NATURE 579.7800(2020):615-+.