Structural basis for genome packaging, retention, and ejection in human cytomegalovirus

doi:10.1038/s41467-021-24820-3

	Structural basis for genome packaging, retention, and ejection in human cytomegalovirus
	Li, Zhihai 1; Pang, Jingjing 1,2; Dong, Lili 1; Yu, Xuekui 1,2
刊名	NATURE COMMUNICATIONS
	2021-07-27
卷号	12 期号:1 页码:14
ISSN号	2041-1723
DOI	10.1038/s41467-021-24820-3
通讯作者	Yu, Xuekui(xkyu@simm.ac.cn)
英文摘要	How the human cytomegalovirus (HCMV) genome-the largest among human herpesviruses-is packaged, retained, and ejected remains unclear. We present the in situ structures of the symmetry-mismatched portal and the capsid vertex-specific components (CVSCs) of HCMV. The 5-fold symmetric 10-helix anchor-uncommon among known portals-contacts the portal-encircling DNA, which is presumed to squeeze the portal as the genome packaging proceeds. We surmise that the 10-helix anchor dampens this action to delay the portal reaching a "head-full" packaging state, thus facilitating the large genome to be packaged. The 6-fold symmetric turret, latched via a coiled coil to a helix from a major capsid protein, supports the portal to retain the packaged genome. CVSCs at the penton vertices-presumed to increase inner capsid pressure-display a low stoichiometry, which would aid genome retention. We also demonstrate that the portal and capsid undergo conformational changes to facilitate genome ejection after viral cell entry. Human cytomegalovirus (HCMV) is the prototypical member of the beta -herpesvirinae subfamily and the leading viral cause of congenital infections that can lead to birth defects and it can also cause life-threatening disease in immunocompromised individuals. Here, the authors present the in-situ cryo-EM structures of the symmetry-mismatched portal and the capsid vertex-specific components (CVSCs) of HCMV and discuss the mechanistic implications for genome package, retention and ejection.
资助项目	100 Talents Program of the Chinese Academy of Sciences ; Natural Science Foundation of Shanghai[18ZR1447700] ; National Natural Science Foundation of China[31900869] ; Shanghai Sailing Program[19YF1456800]
WOS关键词	HERPES-SIMPLEX ; TERMINASE SUBUNITS ; DNA ; PROTEIN ; INFECTION ; MANIFESTATIONS ; PREDICTION ; STABILITY ; CLEAVAGE ; COMPLEX
WOS研究方向	Science & Technology - Other Topics
语种	英语
出版者	NATURE PORTFOLIO
WOS记录号	WOS:000683367300001
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/297661]
专题	中国科学院上海药物研究所
通讯作者	Yu, Xuekui
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, Cryoelectron Microscopy Res Ctr, Shanghai, Peoples R China 2.Univ Chinese Acad Sci, Beijing, Peoples R China
推荐引用方式 GB/T 7714	Li, Zhihai,Pang, Jingjing,Dong, Lili,et al. Structural basis for genome packaging, retention, and ejection in human cytomegalovirus[J]. NATURE COMMUNICATIONS,2021,12(1):14.
APA	Li, Zhihai,Pang, Jingjing,Dong, Lili,&Yu, Xuekui.(2021).Structural basis for genome packaging, retention, and ejection in human cytomegalovirus.NATURE COMMUNICATIONS,12(1),14.
MLA	Li, Zhihai,et al."Structural basis for genome packaging, retention, and ejection in human cytomegalovirus".NATURE COMMUNICATIONS 12.1(2021):14.