Potent anti-influenza H7 human monoclonal antibody induces separation of hemagglutinin receptor-binding head domains.

Abstract:

:Seasonal influenza virus infections can cause significant morbidity and mortality, but the threat from the emergence of a new pandemic influenza strain might have potentially even more devastating consequences. As such, there is intense interest in isolating and characterizing potent neutralizing antibodies that target the hemagglutinin (HA) viral surface glycoprotein. Here, we use cryo-electron microscopy (cryoEM) to decipher the mechanism of action of a potent HA head-directed monoclonal antibody (mAb) bound to an influenza H7 HA. The epitope of the antibody is not solvent accessible in the compact, prefusion conformation that typifies all HA structures to date. Instead, the antibody binds between HA head protomers to an epitope that must be partly or transiently exposed in the prefusion conformation. The "breathing" of the HA protomers is implied by the exposure of this epitope, which is consistent with metastability of class I fusion proteins. This structure likely therefore represents an early structural intermediate in the viral fusion process. Understanding the extent of transient exposure of conserved neutralizing epitopes also may lead to new opportunities to combat influenza that have not been appreciated previously.

journal_name

PLoS Biol

journal_title

PLoS biology

authors

Turner HL,Pallesen J,Lang S,Bangaru S,Urata S,Li S,Cottrell CA,Bowman CA,Crowe JE Jr,Wilson IA,Ward AB

doi

10.1371/journal.pbio.3000139

subject

Has Abstract

pub_date

2019-02-04 00:00:00

pages

e3000139

issue

2

eissn

1544-9173

issn

1545-7885

pii

PBIOLOGY-D-18-00830

journal_volume

17

pub_type

杂志文章
  • The homeostatic dynamics of feeding behaviour identify novel mechanisms of anorectic agents.

    abstract::Better understanding of feeding behaviour will be vital in reducing obesity and metabolic syndrome, but we lack a standard model that captures the complexity of feeding behaviour. We construct an accurate stochastic model of rodent feeding at the bout level in order to perform quantitative behavioural analysis. Analys...

    journal_title:PLoS biology

    pub_type: 杂志文章

    doi:10.1371/journal.pbio.3000482

    authors: McGrath TM,Spreckley E,Rodriguez AF,Viscomi C,Alamshah A,Akalestou E,Murphy KG,Jones NS

    更新日期:2019-12-05 00:00:00

  • Stable T-bet(+)GATA-3(+) Th1/Th2 hybrid cells arise in vivo, can develop directly from naive precursors, and limit immunopathologic inflammation.

    abstract::Differentiated T helper (Th) cell lineages are thought to emerge from alternative cell fate decisions. However, recent studies indicated that differentiated Th cells can adopt mixed phenotypes during secondary immunological challenges. Here we show that natural primary immune responses against parasites generate bifun...

    journal_title:PLoS biology

    pub_type: 杂志文章

    doi:10.1371/journal.pbio.1001633

    authors: Peine M,Rausch S,Helmstetter C,Fröhlich A,Hegazy AN,Kühl AA,Grevelding CG,Höfer T,Hartmann S,Löhning M

    更新日期:2013-01-01 00:00:00

  • MicroRNA-driven developmental remodeling in the brain distinguishes humans from other primates.

    abstract::While multiple studies have reported the accelerated evolution of brain gene expression in the human lineage, the mechanisms underlying such changes are unknown. Here, we address this issue from a developmental perspective, by analyzing mRNA and microRNA (miRNA) expression in two brain regions within macaques, chimpan...

    journal_title:PLoS biology

    pub_type: 杂志文章

    doi:10.1371/journal.pbio.1001214

    authors: Somel M,Liu X,Tang L,Yan Z,Hu H,Guo S,Jiang X,Zhang X,Xu G,Xie G,Li N,Hu Y,Chen W,Pääbo S,Khaitovich P

    更新日期:2011-12-01 00:00:00

  • mRNA association by aminoacyl tRNA synthetase occurs at a putative anticodon mimic and autoregulates translation in response to tRNA levels.

    abstract::Aminoacyl-tRNA synthetases (aaRSs) are well studied for their role in binding and charging tRNAs with cognate amino acids. Recent RNA interactome studies had suggested that these enzymes can also bind polyadenylated RNAs. Here, we explored the mRNA repertoire bound by several yeast aaRSs. RNA immunoprecipitation (RIP)...

    journal_title:PLoS biology

    pub_type: 杂志文章

    doi:10.1371/journal.pbio.3000274

    authors: Levi O,Arava Y

    更新日期:2019-05-17 00:00:00

  • Comparative Developmental Transcriptomics Reveals Rewiring of a Highly Conserved Gene Regulatory Network during a Major Life History Switch in the Sea Urchin Genus Heliocidaris.

    abstract::The ecologically significant shift in developmental strategy from planktotrophic (feeding) to lecithotrophic (nonfeeding) development in the sea urchin genus Heliocidaris is one of the most comprehensively studied life history transitions in any animal. Although the evolution of lecithotrophy involved substantial chan...

    journal_title:PLoS biology

    pub_type: 杂志文章

    doi:10.1371/journal.pbio.1002391

    authors: Israel JW,Martik ML,Byrne M,Raff EC,Raff RA,McClay DR,Wray GA

    更新日期:2016-03-04 00:00:00

  • Parallel evolutionary dynamics of adaptive diversification in Escherichia coli.

    abstract::The causes and mechanisms of evolutionary diversification are central issues in biology. Geographic isolation is the traditional explanation for diversification, but recent theoretical and empirical studies have shown that frequency-dependent selection can drive diversification without isolation and that adaptive dive...

    journal_title:PLoS biology

    pub_type: 杂志文章

    doi:10.1371/journal.pbio.1001490

    authors: Herron MD,Doebeli M

    更新日期:2013-01-01 00:00:00

  • An early role for WNT signaling in specifying neural patterns of Cdx and Hox gene expression and motor neuron subtype identity.

    abstract::The link between extrinsic signaling, progenitor cell specification and neuronal subtype identity is central to the developmental organization of the vertebrate central nervous system. In the hindbrain and spinal cord, distinctions in the rostrocaudal identity of progenitor cells are associated with the generation of ...

    journal_title:PLoS biology

    pub_type: 杂志文章

    doi:10.1371/journal.pbio.0040252

    authors: Nordström U,Maier E,Jessell TM,Edlund T

    更新日期:2006-07-01 00:00:00

  • Cell aging preserves cellular immortality in the presence of lethal levels of damage.

    abstract::Cellular aging, a progressive functional decline driven by damage accumulation, often culminates in the mortality of a cell lineage. Certain lineages, however, are able to sustain long-lasting immortality, as prominently exemplified by stem cells. Here, we show that Escherichia coli cell lineages exhibit comparable pa...

    journal_title:PLoS biology

    pub_type: 杂志文章

    doi:10.1371/journal.pbio.3000266

    authors: Proenca AM,Rang CU,Qiu A,Shi C,Chao L

    更新日期:2019-05-23 00:00:00

  • How Salmonella survives the macrophage's acid attack.

    abstract::Instead of combating the acidification of the host cell vacuole, Salmonella acidifies its own cytoplasm in response to the low extracellular pH, helping it to secrete effector molecules. ...

    journal_title:PLoS biology

    pub_type: 评论,杂志文章

    doi:10.1371/journal.pbio.1002117

    authors: Richardson LA

    更新日期:2015-04-14 00:00:00

  • Variable transcription factor binding: a mechanism of evolutionary change.

    abstract::This primer discusses a study from Bradley et al. in which changes in transcription factor binding between two Drosophila species are revealed by chromatin immunoprecipitation and high-throughput sequencing. ...

    journal_title:PLoS biology

    pub_type: 杂志文章

    doi:10.1371/journal.pbio.1000342

    authors: Wittkopp PJ

    更新日期:2010-03-23 00:00:00

  • Pre-steady-state decoding of the Bicoid morphogen gradient.

    abstract::Morphogen gradients are established by the localized production and subsequent diffusion of signaling molecules. It is generally assumed that cell fates are induced only after morphogen profiles have reached their steady state. Yet, patterning processes during early development occur rapidly, and tissue patterning may...

    journal_title:PLoS biology

    pub_type: 杂志文章

    doi:10.1371/journal.pbio.0050046

    authors: Bergmann S,Sandler O,Sberro H,Shnider S,Schejter E,Shilo BZ,Barkai N

    更新日期:2007-02-01 00:00:00

  • The molecular basis for recognition of CD1d/α-galactosylceramide by a human non-Vα24 T cell receptor.

    abstract::CD1d-mediated presentation of glycolipid antigens to T cells is capable of initiating powerful immune responses that can have a beneficial impact on many diseases. Molecular analyses have recently detailed the lipid antigen recognition strategies utilized by the invariant Vα24-Jα18 TCR rearrangements of iNKT cells, wh...

    journal_title:PLoS biology

    pub_type: 杂志文章

    doi:10.1371/journal.pbio.1001412

    authors: López-Sagaseta J,Kung JE,Savage PB,Gumperz J,Adams EJ

    更新日期:2012-01-01 00:00:00

  • Premitotic assembly of human CENPs -T and -W switches centromeric chromatin to a mitotic state.

    abstract::Centromeres are differentiated chromatin domains, present once per chromosome, that direct segregation of the genome in mitosis and meiosis by specifying assembly of the kinetochore. They are distinct genetic loci in that their identity in most organisms is determined not by the DNA sequences they are associated with,...

    journal_title:PLoS biology

    pub_type: 杂志文章

    doi:10.1371/journal.pbio.1001082

    authors: Prendergast L,van Vuuren C,Kaczmarczyk A,Doering V,Hellwig D,Quinn N,Hoischen C,Diekmann S,Sullivan KF

    更新日期:2011-06-01 00:00:00

  • Rapid antigen diversification through mitotic recombination in the human malaria parasite Plasmodium falciparum.

    abstract::Malaria parasites possess the remarkable ability to maintain chronic infections that fail to elicit a protective immune response, characteristics that have stymied vaccine development and cause people living in endemic regions to remain at risk of malaria despite previous exposure to the disease. These traits stem fro...

    journal_title:PLoS biology

    pub_type: 杂志文章

    doi:10.1371/journal.pbio.3000271

    authors: Zhang X,Alexander N,Leonardi I,Mason C,Kirkman LA,Deitsch KW

    更新日期:2019-05-13 00:00:00

  • A Speculative History of DNA: What If Oswald Avery Had Died in 1934?

    abstract::This speculative Essay explores the consequences of the imagined premature death of Oswald Avery, who in 1944 provided evidence that genes are made of DNA. Four imaginary alternate routes to the genetic function of DNA are outlined, each of which highlights different aspects of the actual process of discovery. ...

    journal_title:PLoS biology

    pub_type: 传,历史文章,杂志文章

    doi:10.1371/journal.pbio.2001197

    authors: Cobb M

    更新日期:2016-12-22 00:00:00

  • BEAF regulates cell-cycle genes through the controlled deposition of H3K9 methylation marks into its conserved dual-core binding sites.

    abstract::Chromatin insulators/boundary elements share the ability to insulate a transgene from its chromosomal context by blocking promiscuous enhancer-promoter interactions and heterochromatin spreading. Several insulating factors target different DNA consensus sequences, defining distinct subfamilies of insulators. Whether e...

    journal_title:PLoS biology

    pub_type: 杂志文章

    doi:10.1371/journal.pbio.0060327

    authors: Emberly E,Blattes R,Schuettengruber B,Hennion M,Jiang N,Hart CM,Käs E,Cuvier O

    更新日期:2008-12-23 00:00:00

  • Polarized Exocytosis Induces Compensatory Endocytosis by Sec4p-Regulated Cortical Actin Polymerization.

    abstract::Polarized growth is maintained by both polarized exocytosis, which transports membrane components to specific locations on the cell cortex, and endocytosis, which retrieves these components before they can diffuse away. Despite functional links between these two transport pathways, they are generally considered to be ...

    journal_title:PLoS biology

    pub_type: 杂志文章

    doi:10.1371/journal.pbio.1002534

    authors: Johansen J,Alfaro G,Beh CT

    更新日期:2016-08-15 00:00:00

  • An Estimate of the Total DNA in the Biosphere.

    abstract::Modern whole-organism genome analysis, in combination with biomass estimates, allows us to estimate a lower bound on the total information content in the biosphere: 5.3 × 1031 (±3.6 × 1031) megabases (Mb) of DNA. Given conservative estimates regarding DNA transcription rates, this information content suggests biospher...

    journal_title:PLoS biology

    pub_type: 杂志文章

    doi:10.1371/journal.pbio.1002168

    authors: Landenmark HK,Forgan DH,Cockell CS

    更新日期:2015-06-11 00:00:00

  • Individual metabolomic signatures of circadian misalignment during simulated night shifts in humans.

    abstract::Misalignment of the daily sleep-wake and fasting-feeding cycles with the endogenous circadian timing system is an inevitable consequence of night shift work and is associated with adverse metabolic health effects. However, a detailed characterisation of the effects of night shifts on 24-h rhythms in the metabolome is ...

    journal_title:PLoS biology

    pub_type: 杂志文章

    doi:10.1371/journal.pbio.3000303

    authors: Kervezee L,Cermakian N,Boivin DB

    更新日期:2019-06-18 00:00:00

  • Modulating brain oscillations to drive brain function.

    abstract::Do neuronal oscillations play a causal role in brain function? In a study in this issue of PLOS Biology, Helfrich and colleagues address this long-standing question by attempting to drive brain oscillations using transcranial electrical current stimulation. Remarkably, they were able to manipulate visual perception by...

    journal_title:PLoS biology

    pub_type: 评论,杂志文章

    doi:10.1371/journal.pbio.1002032

    authors: Thut G

    更新日期:2014-12-30 00:00:00

  • Bistable expression of virulence genes in salmonella leads to the formation of an antibiotic-tolerant subpopulation.

    abstract::Phenotypic heterogeneity can confer clonal groups of organisms with new functionality. A paradigmatic example is the bistable expression of virulence genes in Salmonella typhimurium, which leads to phenotypically virulent and phenotypically avirulent subpopulations. The two subpopulations have been shown to divide lab...

    journal_title:PLoS biology

    pub_type: 杂志文章

    doi:10.1371/journal.pbio.1001928

    authors: Arnoldini M,Vizcarra IA,Peña-Miller R,Stocker N,Diard M,Vogel V,Beardmore RE,Hardt WD,Ackermann M

    更新日期:2014-08-19 00:00:00

  • Functional dissection of an innate immune response by a genome-wide RNAi screen.

    abstract::The innate immune system is ancient and highly conserved. It is the first line of defense and the only recognizable immune system in the vast majority of metazoans. Signaling events that convert pathogen detection into a defense response are central to innate immunity. Drosophila has emerged as an invaluable model org...

    journal_title:PLoS biology

    pub_type: 杂志文章

    doi:10.1371/journal.pbio.0020203

    authors: Foley E,O'Farrell PH

    更新日期:2004-08-01 00:00:00

  • Hippocampal cells integrate past memory and present perception for the future.

    abstract::The ability to use stored information in a highly flexible manner is a defining feature of the declarative memory system. However, the neuronal mechanisms underlying this flexibility are poorly understood. To address this question, we recorded single-unit activity from the hippocampus of 2 nonhuman primates performing...

    journal_title:PLoS biology

    pub_type: 杂志文章

    doi:10.1371/journal.pbio.3000876

    authors: Yang C,Naya Y

    更新日期:2020-11-18 00:00:00

  • Shellfish dredging pushes a flexible avian top predator out of a marine protected area.

    abstract::There is a widespread concern about the direct and indirect effects of industrial fisheries; this concern is particularly pertinent for so-called "marine protected areas" (MPAs), which should be safeguarded by national and international law. The intertidal flats of the Dutch Wadden Sea are a State Nature Monument and ...

    journal_title:PLoS biology

    pub_type: 杂志文章

    doi:10.1371/journal.pbio.0040376

    authors: van Gils JA,Piersma T,Dekinga A,Spaans B,Kraan C

    更新日期:2006-11-01 00:00:00

  • A genetic basis for mechanosensory traits in humans.

    abstract::In all vertebrates hearing and touch represent two distinct sensory systems that both rely on the transformation of mechanical force into electrical signals. There is an extensive literature describing single gene mutations in humans that cause hearing impairment, but there are essentially none for touch. Here we firs...

    journal_title:PLoS biology

    pub_type: 杂志文章

    doi:10.1371/journal.pbio.1001318

    authors: Frenzel H,Bohlender J,Pinsker K,Wohlleben B,Tank J,Lechner SG,Schiska D,Jaijo T,Rüschendorf F,Saar K,Jordan J,Millán JM,Gross M,Lewin GR

    更新日期:2012-01-01 00:00:00

  • Short Time-Scale Sensory Coding in S1 during Discrimination of Whisker Vibrotactile Sequences.

    abstract::Rodent whisker input consists of dense microvibration sequences that are often temporally integrated for perceptual discrimination. Whether primary somatosensory cortex (S1) participates in temporal integration is unknown. We trained rats to discriminate whisker impulse sequences that varied in single-impulse kinemati...

    journal_title:PLoS biology

    pub_type: 杂志文章

    doi:10.1371/journal.pbio.1002549

    authors: McGuire LM,Telian G,Laboy-Juárez KJ,Miyashita T,Lee DJ,Smith KA,Feldman DE

    更新日期:2016-08-30 00:00:00

  • Functional implications of sleep development.

    abstract::Why do we sleep? The sleep patterns and mechanisms that occur throughout development may give us a clue. ...

    journal_title:PLoS biology

    pub_type: 杂志文章

    doi:10.1371/journal.pbio.0030178

    authors: Siegel JM

    更新日期:2005-05-01 00:00:00

  • Transcriptional control in the segmentation gene network of Drosophila.

    abstract::The segmentation gene network of Drosophila consists of maternal and zygotic factors that generate, by transcriptional (cross-) regulation, expression patterns of increasing complexity along the anterior-posterior axis of the embryo. Using known binding site information for maternal and zygotic gap transcription facto...

    journal_title:PLoS biology

    pub_type: 杂志文章

    doi:10.1371/journal.pbio.0020271

    authors: Schroeder MD,Pearce M,Fak J,Fan H,Unnerstall U,Emberly E,Rajewsky N,Siggia ED,Gaul U

    更新日期:2004-09-01 00:00:00

  • Imre Festetics and the Sheep Breeders' Society of Moravia: Mendel's Forgotten "Research Network".

    abstract::Contemporary science thrives on collaborative networks, but these can also be found elsewhere in the history of science in unexpected places. When Mendel turned his attention to inheritance in peas he was not an isolated monk, but rather the latest in a line of Moravian researchers and agriculturalists who had been th...

    journal_title:PLoS biology

    pub_type: 历史文章,杂志文章

    doi:10.1371/journal.pbio.1001772

    authors: Poczai P,Bell N,Hyvönen J

    更新日期:2014-01-01 00:00:00

  • Identification and functional characterization of N-terminally acetylated proteins in Drosophila melanogaster.

    abstract::Protein modifications play a major role for most biological processes in living organisms. Amino-terminal acetylation of proteins is a common modification found throughout the tree of life: the N-terminus of a nascent polypeptide chain becomes co-translationally acetylated, often after the removal of the initiating me...

    journal_title:PLoS biology

    pub_type: 杂志文章

    doi:10.1371/journal.pbio.1000236

    authors: Goetze S,Qeli E,Mosimann C,Staes A,Gerrits B,Roschitzki B,Mohanty S,Niederer EM,Laczko E,Timmerman E,Lange V,Hafen E,Aebersold R,Vandekerckhove J,Basler K,Ahrens CH,Gevaert K,Brunner E

    更新日期:2009-11-01 00:00:00