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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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
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Journal ArticleDOI
The mechanisms controlling the recognition of tumor and virus infected cells by NKp46
Tal I. Arnon,Hagit Achdout,Hagit Achdout,Niva Lieberman,Niva Lieberman,Roi Gazit,Roi Gazit,Tsufit Gonen-Gross,Tsufit Gonen-Gross,Gil Katz,Gil Katz,Ahuva Bar-Ilan,Ahuva Bar-Ilan,Noga Bloushtain,Noga Bloushtain,Marianna Lev,Marianna Lev,Aviva Joseph,Aviva Joseph,Eli Kedar,Eli Kedar,Angel Porgador,Angel Porgador,Ofer Mandelboim,Ofer Mandelboim +24 more
TL;DR: It is established that the ability of NK p46 to recognize target cells is confined to the membrane proximal domain, and largely relies on the highly conserved sugar-carrying residue, Thr 225, which plays a critical dual role in NKp46 interactions with both viral hemagglutinins and the unknown tumor ligands via different mechanisms.
Journal ArticleDOI
Inhibition of Influenza Virus Infection by Multivalent Sialic‐Acid‐Functionalized Gold Nanoparticles
Ilona Papp,Christian Sieben,Kai Ludwig,Meike Roskamp,Christoph Böttcher,Sabine Schlecht,Andreas Herrmann,Rainer Haag +7 more
TL;DR: An efficient synthesis of sialic-acid-terminated glycerol dendron to chemically functionalize 2 nm and 14 nm gold nanoparticles (AuNPs) is described, which allows a new type of molecular-imaging activity-correlation and is of particular relevance for further application in alternative antiviral therapy.
Journal ArticleDOI
THE ORIGINS OF NEW PANDEMIC VIRUSES: The Acquisition of New Host Ranges by Canine Parvovirus and Influenza A Viruses
TL;DR: Transfer of viruses between hosts to create a new self-sustaining epidemic is rare; however, those new viruses can cause severe outbreaks and examples of such viruses include three pandemic human influenza A viruses and canine parvovirus in dogs.
Journal ArticleDOI
Taking geometry to its edge: fast unbound rigid (and hinge-bent) docking.
Dina Schneidman-Duhovny,Yuval Inbar,Vladimir Polak,Maxim Shatsky,Inbal Halperin,Hadar Benyamini,Adi Barzilai,Oranit Dror,Nurit Haspel,Ruth Nussinov,Ruth Nussinov,Haim J. Wolfson +11 more
TL;DR: A very efficient rigid “unbound” soft docking methodology, which is based on detection of geometric shape complementarity, allowing liberal steric clash at the interface, avoiding the exhaustive search of the 6D transformation space.
Journal ArticleDOI
The role of receptor binding specificity in interspecies transmission of influenza viruses.
Masaki Imai,Yoshihiro Kawaoka +1 more
TL;DR: The receptor binding specificity of influenza A viruses is discussed and its role in interspecies transmission is discussed.
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.
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.
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Structure of the haemagglutinin membrane glycoprotein of influenza virus at 3 A resolution.
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