Structural transitions in influenza haemagglutinin at membrane fusion pH

doi:10.1038/s41586-020-2333-6

GSTDTAP > 地球科学

DOI	10.1038/s41586-020-2333-6
	Structural transitions in influenza haemagglutinin at membrane fusion pH
	Wei, Kevin 1,2; Korsunsky, Ilya 1,2,3,4,5,6; Marshall, Jennifer L.7,8; Gao, Anqi 1,2; Watts, Gerald F. M.1,2; Major, Triin 7; Croft, Adam P.7,8; Watts, Jordan 1,2; Blazar, Philip E.9; Lange, Jeffrey K.9; Thornhill, Thomas S.9; Filer, Andrew 7,8; Raza, Karim 7,8; Donlin, Laura T.10; Siebel, Christian W.11
	2020-04-22
发表期刊	NATURE
ISSN	0028-0836
EISSN	1476-4687
出版年	2020
卷号	583 期号:7814 页码:150-+
文章类型	Article
语种	英语
国家	England
英文关键词	Cryo-electron microscopy studies of the influenza haemagglutinin glycoprotein at the low pH of host endosomes reveals structural intermediates, offering a dynamic view of how the protein mediates membrane fusion. Infection by enveloped viruses involves fusion of their lipid envelopes with cellular membranes to release the viral genome into cells. For HIV, Ebola, influenza and numerous other viruses, envelope glycoproteins bind the infecting virion to cell-surface receptors and mediate membrane fusion. In the case of influenza, the receptor-binding glycoprotein is the haemagglutinin (HA), and following receptor-mediated uptake of the bound virus by endocytosis(1), it is the HA that mediates fusion of the virus envelope with the membrane of the endosome(2). Each subunit of the trimeric HA consists of two disulfide-linked polypeptides, HA1 and HA2. The larger, virus-membrane-distal, HA1 mediates receptor binding the smaller, membrane-proximal, HA2 anchors HA in the envelope and contains the fusion peptide, a region that is directly involved in membrane interaction(3). The low pH of endosomes activates fusion by facilitating irreversible conformational changes in the glycoprotein. The structures of the initial HA at neutral pH and the final HA at fusion pH have been investigated by electron microscopy(4,5) and X-ray crystallography(6-8). Here, to further study the process of fusion, we incubate HA for different times at pH 5.0 and directly image structural changes using single-particle cryo-electron microscopy. We describe three distinct, previously undescribed forms of HA, most notably a 150 angstrom-long triple-helical coil of HA2, which may bridge between the viral and endosomal membranes. Comparison of these structures reveals concerted conformational rearrangements through which the HA mediates membrane fusion.
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:000535878900005
WOS关键词	BEAM-INDUCED MOTION ; VIRUS HEMAGGLUTININ ; BAYESIAN-APPROACH ; RECEPTOR-BINDING ; GLYCOPROTEIN ; EVOLUTION ; PEPTIDE
WOS类目	Multidisciplinary Sciences
WOS研究方向	Science & Technology - Other Topics
引用统计	被引频次：113[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	http://119.78.100.173/C666/handle/2XK7JSWQ/281546
专题	地球科学资源环境科学气候变化
作者单位	1.Brigham & Womens Hosp, Div Rheumatol Inflammat & Immun, 75 Francis St, Boston, MA 02115 USA; 2.Harvard Med Sch, Boston, MA 02115 USA; 3.Brigham & Womens Hosp, Ctr Data Sci, 75 Francis St, Boston, MA 02115 USA; 4.Brigham & Womens Hosp, Dept Med, Div Genet, 75 Francis St, Boston, MA 02115 USA; 5.Harvard Med Sch, Dept Biomed Informat, Boston, MA 02115 USA; 6.Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA 02142 USA; 7.Univ Birmingham, NIHR Birmingham Biomed Res Ctr, Inst Inflammat & Ageing, Rheumatol Res Grp,Queen Elizabeth Hosp, Birmingham, W Midlands, England; 8.Univ Birmingham, Queen Elizabeth Hosp, Clin Res Facil, Birmingham, W Midlands, England; 9.Brigham & Womens Hosp, Dept Orthoped Surg, 75 Francis St, Boston, MA 02115 USA; 10.Hosp Special Surg, Arthrit & Tissue Degenerat, 535 E 70th St, New York, NY 10021 USA; 11.Genentech Inc, Dept Discovery Oncol, San Francisco, CA USA; 12.Univ Oxford, Kennedy Inst Rheumatol, Oxford, England; 13.Univ Manchester, Manchester Acad Hlth Sci Ctr, Ctr Musculoskeletal Res, Ctr Genet & Genom Versus Arthrit, Manchester, Lancs, England
推荐引用方式 GB/T 7714	Wei, Kevin,Korsunsky, Ilya,Marshall, Jennifer L.,et al. Structural transitions in influenza haemagglutinin at membrane fusion pH[J]. NATURE,2020,583(7814):150-+.
APA	Wei, Kevin.,Korsunsky, Ilya.,Marshall, Jennifer L..,Gao, Anqi.,Watts, Gerald F. M..,...&Siebel, Christian W..(2020).Structural transitions in influenza haemagglutinin at membrane fusion pH.NATURE,583(7814),150-+.
MLA	Wei, Kevin,et al."Structural transitions in influenza haemagglutinin at membrane fusion pH".NATURE 583.7814(2020):150-+.