Structure of the human metapneumovirus polymerase phosphoprotein complex

doi:10.1038/s41586-019-1759-1

GSTDTAP > 地球科学

DOI	10.1038/s41586-019-1759-1
	Structure of the human metapneumovirus polymerase phosphoprotein complex
	Pan, Junhua 1,2; Qian, Xinlei 3,4,5; Lattmann, Simon 4; El Sahili, Abbas 3,4; Yeo, Tiong Han 3; Jia, Huan 3,4; Cressey, Tessa 6; Ludeke, Barbara 6; Noton, Sarah 6; Kalocsay, Marian 7; Fearns, Rachel 6; Lescar, Julien 3,4,5
	2020-05-01
发表期刊	NATURE
ISSN	0028-0836
EISSN	1476-4687
出版年	2020
卷号	577 期号:7789 页码:275-+
文章类型	Article
语种	英语
国家	USA; Singapore
英文关键词	Respiratory syncytial virus (RSV) and human metapneumovirus (HMPV) cause severe respiratory diseases in infants and elderly adults(1). No vaccine or effective antiviral therapy currently exists to control RSV or HMPV infections. During viral genome replication and transcription, the tetrameric phosphoprotein P serves as a crucial adaptor between the ribonucleoprotein template and the L protein, which has RNA-dependent RNA polymerase (RdRp), GDP polyribonucleotidyltransferase and cap-specific methyltransferase activities(2,3). How P interacts with L and mediates the association with the free form of N and with the ribonucleoprotein is not clear for HMPV or other major human pathogens, including the viruses that cause measles, Ebola and rabies. Here we report a cryo-electron microscopy reconstruction that shows the ring-shaped structure of the polymerase and capping domains of HMPV-L bound to a tetramer of P. The connector and methyltransferase domains of L are mobile with respect to the core. The putative priming loop that is important for the initiation of RNA synthesis is fully retracted, which leaves space in the active-site cavity for RNA elongation. P interacts extensively with the N-terminal region of L, burying more than 4,016 angstrom(2) of the molecular surface area in the interface. Two of the four helices that form the coiled-coil tetramerization domain of P, and long C-terminal extensions projecting from these two helices, wrap around the L protein in a manner similar to tentacles. The structural versatility of the four P protomers-which are largely disordered in their free state-demonstrates an example of a ' folding-upon-partner-binding' mechanism for carrying out P adaptor functions. The structure shows that P has the potential to modulate multiple functions of L and these results should accelerate the design of specific antiviral drugs.
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:000506682500048
WOS关键词	VESICULAR STOMATITIS-VIRUS ; L PROTEIN ; RNA ; SEQUENCE ; DOMAIN ; PHOSPHORYLATION ; REPLICATION ; FEATURES ; M2-1
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/281144
专题	地球科学资源环境科学气候变化
作者单位	1.Boston Childrens Hosp, Div Mol Med, Boston, MA 02115 USA; 2.Harvard Med Sch, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA; 3.Nanyang Technol Univ, Sch Biol Sci, Singapore, Singapore; 4.Nanyang Technol Univ, NTU Inst Struct Biol, Singapore, Singapore; 5.Singapore MIT Alliance Res & Technol, Antimicrobial Resistance Interdisciplinary Res Gr, Singapore, Singapore; 6.Boston Univ, Sch Med, Natl Emerging Infect Dis Labs Boston, Boston, MA 02118 USA; 7.Harvard Med Sch, Dept Syst Biol, Lab Syst Pharmacol, Boston, MA 02115 USA
推荐引用方式 GB/T 7714	Pan, Junhua,Qian, Xinlei,Lattmann, Simon,et al. Structure of the human metapneumovirus polymerase phosphoprotein complex[J]. NATURE,2020,577(7789):275-+.
APA	Pan, Junhua.,Qian, Xinlei.,Lattmann, Simon.,El Sahili, Abbas.,Yeo, Tiong Han.,...&Lescar, Julien.(2020).Structure of the human metapneumovirus polymerase phosphoprotein complex.NATURE,577(7789),275-+.
MLA	Pan, Junhua,et al."Structure of the human metapneumovirus polymerase phosphoprotein complex".NATURE 577.7789(2020):275-+.