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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Identification of a structural motif crucial for infectivity of hepatitis B viruses
Lars Stoeckl,Anneke Funk,Ariane Kopitzki,Boerries Brandenburg,Stefanie Oess,Hans Will,Hüseyin Sirma,Eberhard Hildt +7 more
TL;DR: An infectious entry mechanism unique for hepadnaviruses is proposed that involves virus internalization by receptor-mediated endocytosis followed by processing of surface protein in endosomes, which activates the function of TLMs that are essential for viral particle translocation through the endosomal membrane into the cytosol and productive infection.
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Monitoring influenza hemagglutinin and glycan interactions using surface plasmon resonance.
TL;DR: The results showed that glycan-HA binding analyses can be performed reliably and efficiently on Biacore-chips in the SPR system, using chemically synthesized biotinylated multivalent-glycans, and suggested that this SPR-based method is suitable for influenza surveillance to define the pandemic scenario as well as to screen of synthetic glycans and other compounds that may interfere with glyCAN-HA interactions.
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Only Two Residues Are Responsible for the Dramatic Difference in Receptor Binding between Swine and New Pandemic H1 Hemagglutinin
Robert P. de Vries,Erik de Vries,Karen S. Moore,Alan Rigter,Peter J. M. Rottier,Cornelis A. M. de Haan +5 more
TL;DR: The results show that closely related swine and new pandemic H1 proteins differ dramatically in their ability to bind these receptors and substitution of both was found to act synergistically and reverse the phenotype almost completely.
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Folding of hepatitis C virus E1 glycoprotein in a cell-free system.
Marcello Merola,Michela Brazzoli,Fabienne Cocchiarella,Jens Heile,Ari Helenius,Amy J. Weiner,Michael Houghton,Sergio Abrignani +7 more
TL;DR: It is concluded that E1 folding is a process that is affected not only by E2, as previously shown, but also by the Core, and the folding of viral proteins can depend on complex interactions between neighboring proteins within the polyprotein precursor.
References
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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.
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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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