Journal ArticleDOI
Receptor Binding and Membrane Fusion in Virus Entry: The Influenza Hemagglutinin
John J. Skehel,Don C. Wiley +1 more
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TLDR
Comparisons to the soluble N-ethyl-maleimide-sensitive factor attachment protein receptor (SNARE) protein complex of vesicle fusion suggests that these molecules are all in the fusion-activated conformation and that the juxtaposition of the membrane anchor and fusion peptide, a recurring feature, is involved in the fused mechanism.Abstract:
Hemagglutinin (HA) is the receptor-binding and membrane fusion glycoprotein of influenza virus and the target for infectivity-neutralizing antibodies. The structures of three conformations of the ectodomain of the 1968 Hong Kong influenza virus HA have been determined by X-ray crystallography: the single-chain precursor, HA0; the metastable neutral-pH conformation found on virus, and the fusion pH-induced conformation. These structures provide a framework for designing and interpreting the results of experiments on the activity of HA in receptor binding, the generation of emerging and reemerging epidemics, and membrane fusion during viral entry. Structures of HA in complex with sialic acid receptor analogs, together with binding experiments, provide details of these low-affinity interactions in terms of the sialic acid substituents recognized and the HA residues involved in recognition. Neutralizing antibody-binding sites surround the receptor-binding pocket on the membrane-distal surface of HA, and the structures of the complexes between neutralizing monoclonal Fabs and HA indicate possible neutralization mechanisms. Cleavage of the biosynthetic precursor HA0 at a prominent loop in its structure primes HA for subsequent activation of membrane fusion at endosomal pH (Figure 1). Priming involves insertion of the fusion peptide into a charged pocket in the precursor; activation requires its extrusion towards the fusion target membrane, as the N terminus of a newly formed trimeric coiled coil, and repositioning of the C-terminal membrane anchor near the fusion peptide at the same end of a rod-shaped molecule. Comparison of this new HA conformation, which has been formed for membrane fusion, with the structures determined for other virus fusion glycoproteins suggests that these molecules are all in the fusion-activated conformation and that the juxtaposition of the membrane anchor and fusion peptide, a recurring feature, is involved in the fusion mechanism. Extension of these comparisons to the soluble N-ethyl-maleimide-sensitive factor attachment protein receptor (SNARE) protein complex of vesicle fusion allows a similar conclusion.read more
Citations
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Journal ArticleDOI
The Ubiquitin‐Vacuolar Protein Sorting System is Selectively Required During Entry of Influenza Virus into Host Cells
TL;DR: It is concluded that influenza virus selectively requires the ubiquitin/vacuolar protein sorting pathway for entry into host cells, and that it must communicate with a specific cellular machinery for intracellular sorting during the initial phase of virus infection.
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Galectin-1 Binds to Influenza Virus and Ameliorates Influenza Virus Pathogenesis
Mei Lin Yang,Yi Chen,Shainn Wei Wang,Yen Jang Huang,Chia Hsing Leu,Nai Chi Yeh,Chun Yen Chu,Chia Cheng Lin,Gia Shing Shieh,Yuh Ling Chen,Jen Ren Wang,Ching-Ho Wang,Chao Liang Wu,Ai Li Shiau +13 more
TL;DR: It is shown for the first time that intranasal treatment of galectin-1 could enhance survival of mice against lethal challenge with influenza virus by reducing viral load, inflammation, and apoptosis in the lung.
Book ChapterDOI
Cell entry of enveloped viruses.
TL;DR: The different envelope glycoprotein structures that viruses develop to achieve membrane fusion and the entry of the virus are summarized and the different entry pathways and cellular proteins that viruses have subverted to allow infection of the cell and the receptors that are used are described.
Journal ArticleDOI
Glyconanoparticles for the plasmonic detection and discrimination between human and avian influenza virus
María J. Marín,Abdul M. Rashid,Martin Rejzek,Shirley A. Fairhurst,Stephen A. Wharton,Stephen R. Martin,John W. McCauley,Thomas Wileman,Robert A. Field,David A. Russell +9 more
TL;DR: The glyconanoparticles were able to discriminate between human ( α2,6 binding) and avian (α2,3 binding) RG14 (H5N1) influenza virus highlighting the binding specificity of the trivalent α 2,6-thio-linked sialic acid ligand.
References
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MOLSCRIPT: a program to produce both detailed and schematic plots of protein structures
TL;DR: The MOLSCRIPT program as discussed by the authors produces plots of protein structures using several different kinds of representations, including simple wire models, ball-and-stick models, CPK models and text labels.
Journal ArticleDOI
Structure of an HIV gp120 envelope glycoprotein in complex with the CD4 receptor and a neutralizing human antibody
Peter D. Kwong,Richard T. Wyatt,James E. Robinson,Raymond W. Sweet,Joseph Sodroski,Wayne A. Hendrickson,Wayne A. Hendrickson +6 more
TL;DR: The structure reveals a cavity-laden CD4–gp120 interface, a conserved binding site for the chemokine receptor, evidence for a conformational change upon CD4 binding, the nature of a CD4-induced antibody epitope, and specific mechanisms for immune evasion.
Journal ArticleDOI
Structure of the haemagglutinin membrane glycoprotein of influenza virus at 3 A resolution.
TL;DR: The haemagglutinin glycoprotein of influenza virus is a trimer comprising two structurally distinct regions: a triple-stranded coiled-coil of α-helices extends 76 Å from the membrane and a globular region of antiparallel β-sheet is positioned on top of this stem.
Journal ArticleDOI
Crystal structure of a SNARE complex involved in synaptic exocytosis at 2.4 Å resolution
TL;DR: The X-ray crystal structure of a core synaptic fusion complex containing syntaxin-1A, synaptobrevin-II and SNAP-25B reveals a highly twisted and parallel four-helix bundle that differs from the bundles described for the haemagglutinin and HIV/SIV gp41 membrane-fusion proteins.
PatentDOI
Core structure of GP41 from the HIV envelope glycoprotein
TL;DR: The crystal structure of this complex, composed of the peptides N36 and C34, is a six-helical bundle that shows striking similarity to the low-pH-induced conformation of influenza hemagglutinin and likely represents the core of fusion-active gp41.
Related Papers (5)
Structure of the haemagglutinin membrane glycoprotein of influenza virus at 3 A resolution.
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