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
Citations
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Journal ArticleDOI
Recent Evolution of Equine Influenza and the Origin of Canine Influenza.
Patrick J. Collins,Sebastien G. Vachieri,Lesley F. Haire,Roksana W. Ogrodowicz,Stephen R. Martin,Philip A. Walker,Xiaoli Xiong,Steven J. Gamblin,John J. Skehel +8 more
TL;DR: To understand the molecular basis of changes in the antigenicity of H3 hemagglutinins (HAs) that have occurred during virus evolution in horses and to investigate the role of HA in the equine to canine cross-species transfer, X-ray crystallography was used.
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Characterization of Influenza Vaccine Immunogenicity Using Influenza Antigen Microarrays
Jordan V. Price,Justin A. Jarrell,David Furman,Nicole H. Kattah,Evan W. Newell,Cornelia L. Dekker,Mark M. Davis,Paul J. Utz +7 more
TL;DR: The developed influenza hemagglutinin whole-protein and peptide microarrays provide powerful tools for rapid and accurate measurement of broad antibody-based immune responses to influenza, and may be useful in measuring response to other vaccines and infectious agents.
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HATRIC-based identification of receptors for orphan ligands.
Nadine Sobotzki,Nadine Sobotzki,Michael A. Schafroth,Alina Rudnicka,Alina Rudnicka,Anika Koetemann,Florian Marty,Sandra Goetze,Yohei Yamauchi,Erick M. Carreira,Bernd Wollscheid +10 more
TL;DR: A mass spectrometry-based ligand receptor capture technology that can identify receptors for a diverse range of ligands at physiological pH with as few as a million cells, and enables the identification of complex extracellular interactomes.
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Bovine lactoferrin-derived peptides as novel broad-spectrum inhibitors of influenza virus.
Maria Grazia Ammendolia,Mariangela Agamennone,Agostina Pietrantoni,Fabio Lannutti,Rosa Anna Siciliano,Beatrice De Giulio,Carla Amici,Fabiana Superti +7 more
TL;DR: Cutting bLf into its C- and N-lobes shows that inhibition of influenza virus hemagglutination and cell infection is entirely attributable to the C-lobe and that all major virus subtypes, including H1N1 and H3N2, are inhibited.
Journal ArticleDOI
Crystal Structure of Glycoprotein C from a Hantavirus in the Post-fusion Conformation.
Shmuel Willensky,Hagit Bar-Rogovsky,Eduardo A Bignon,Nicole D. Tischler,Yorgo Modis,Moshe Dessau +5 more
TL;DR: The crystal structure of glycoprotein C (GC) from Puumala virus (PUUV), a representative member of the Hantavirus genus, is presented and it shows GC as the membrane fusion effector of PUUV and it presents a class II membrane fusion protein fold.
References
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Journal ArticleDOI
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.
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Structure of the haemagglutinin membrane glycoprotein of influenza virus at 3 A resolution.
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