Abstract:
:Targeting of immunoglobulin E (IgE) represents an interesting approach for the treatment of allergic disorders. A high-affinity monoclonal anti-IgE antibody, ligelizumab, has recently been developed to overcome some of the limitations associated with the clinical use of the therapeutic anti-IgE antibody, omalizumab. Here, we determine the molecular binding profile and functional modes-of-action of ligelizumab. We solve the crystal structure of ligelizumab bound to IgE, and report epitope differences between ligelizumab and omalizumab that contribute to their qualitatively distinct IgE-receptor inhibition profiles. While ligelizumab shows superior inhibition of IgE binding to FcεRI, basophil activation, IgE production by B cells and passive systemic anaphylaxis in an in vivo mouse model, ligelizumab is less potent in inhibiting IgE:CD23 interactions than omalizumab. Our data thus provide a structural and mechanistic foundation for understanding the efficient suppression of FcεRI-dependent allergic reactions by ligelizumab in vitro as well as in vivo.
journal_name
Nat Communjournal_title
Nature communicationsauthors
Gasser P,Tarchevskaya SS,Guntern P,Brigger D,Ruppli R,Zbären N,Kleinboelting S,Heusser C,Jardetzky TS,Eggel Adoi
10.1038/s41467-019-13815-wsubject
Has Abstractpub_date
2020-01-08 00:00:00pages
165issue
1issn
2041-1723pii
10.1038/s41467-019-13815-wjournal_volume
11pub_type
杂志文章abstract::LPMO (lytic polysaccharide monooxygenase) represents a unique paradigm of cellulosic biomass degradation by an oxidative mechanism. Understanding the role of LPMO in deconstructing crystalline cellulose is fundamental to the enzyme's biological function and will help to specify the use of LPMO in biorefinery applicati...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-017-01028-y
更新日期:2017-10-12 00:00:00
abstract::Plasma wakefield accelerators have been used to accelerate electron and positron particle beams with gradients that are orders of magnitude larger than those achieved in conventional accelerators. In addition to being accelerated by the plasma wakefield, the beam particles also experience strong transverse forces that...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms11785
更新日期:2016-06-02 00:00:00
abstract::The ability to identify cause-effect relations is an essential component of the scientific method. The identification of causal relations is generally accomplished through statistical trials where alternative hypotheses are tested against each other. Traditionally, such trials have been based on classical statistics. ...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-019-09383-8
更新日期:2019-04-01 00:00:00
abstract::Land-atmosphere exchanges influence atmospheric CO2. Emphasis has been on describing photosynthetic CO2 uptake, but less on respiration losses. New global datasets describe upper canopy dark respiration (R d) and temperature dependencies. This allows characterisation of baseline R d, instantaneous temperature response...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-017-01774-z
更新日期:2017-11-17 00:00:00
abstract::Neurotransmitter/sodium symporters (NSSs) are responsible for Na+-dependent reuptake of neurotransmitters and represent key targets for antidepressants and psychostimulants. LeuT, a prokaryotic NSS protein, constitutes a primary structural model for these transporters. Here we show that K+ inhibits Na+-dependent bindi...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms12755
更新日期:2016-09-28 00:00:00
abstract::Many bacteria can exchange genetic material through horizontal gene transfer (HGT) mediated by plasmids and plasmid-borne transposable elements. Here, we study the population structure and dynamics of over 10,000 bacterial plasmids, by quantifying their genetic similarities and reconstructing a network based on their ...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-020-16282-w
更新日期:2020-05-15 00:00:00
abstract::Despite centuries of research, much about the barbarian migrations that took place between the fourth and sixth centuries in Europe remains hotly debated. To better understand this key era that marks the dawn of modern European societies, we obtained ancient genomic DNA from 63 samples from two cemeteries (from Hungar...
journal_title:Nature communications
pub_type: 历史文章,杂志文章
doi:10.1038/s41467-018-06024-4
更新日期:2018-09-11 00:00:00
abstract::Previous genome-wide association studies (GWASs) have shown that common genetic variation contributes to the heritable risk of glioma. To identify new glioma susceptibility loci, we conducted a meta-analysis of four GWAS (totalling 4,147 cases and 7,435 controls), with imputation using 1000 Genomes and UK10K Project d...
journal_title:Nature communications
pub_type: 杂志文章,meta分析
doi:10.1038/ncomms9559
更新日期:2015-10-01 00:00:00
abstract::Biochemical investigation of protein phosphorylation events is limited by inefficient production of the phosphorylated and non-phosphorylated forms of full-length proteins. Here using a genomically recoded strain of E. coli with a flexible UAG codon we produce site-specific serine- or phosphoserine-containing proteins...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms9130
更新日期:2015-09-09 00:00:00
abstract::FAM46C is one of the most frequently mutated genes in multiple myeloma. Here, using a combination of in vitro and in vivo approaches, we demonstrate that FAM46C encodes an active non-canonical poly(A) polymerase which enhances mRNA stability and gene expression. Reintroduction of active FAM46C into multiple myeloma ce...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-017-00578-5
更新日期:2017-09-20 00:00:00
abstract::SCRaMbLE (Synthetic Chromosome Rearrangement and Modification by LoxP-mediated Evolution) is a genome restructuring technique that can be used in synthetic genomes such as that of Sc2.0, the synthetic yeast genome, which contains hundreds to thousands of strategically positioned loxPsym sites. SCRaMbLE has been used t...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-018-04157-0
更新日期:2018-05-22 00:00:00
abstract::Acute otitis media (AOM) is among the most common pediatric diseases, and the most frequent reason for antibiotic treatment in children. Risk of AOM is dependent on environmental and host factors, as well as a significant genetic component. We identify genome-wide significance at a locus on 6q25.3 (rs2932989, Pmeta=2....
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms12792
更新日期:2016-09-28 00:00:00
abstract::Type I interferons (IFN) are being rediscovered as potent anti-tumoral agents. Activation of the STimulator of INterferon Genes (STING) by DMXAA (5,6-dimethylxanthenone-4-acetic acid) can induce strong production of IFNα/β and rejection of transplanted primary tumors. In the present study, we address whether targeting...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-019-11998-w
更新日期:2019-09-11 00:00:00
abstract::Impaired lung function is often caused by cigarette smoking, making it challenging to disentangle its role in lung cancer susceptibility. Investigation of the shared genetic basis of these phenotypes in the UK Biobank and International Lung Cancer Consortium (29,266 cases, 56,450 controls) shows that lung cancer is ge...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-019-13855-2
更新日期:2020-01-07 00:00:00
abstract::Natural systems frequently exploit intricate multiscale and multiphasic structures to achieve functionalities beyond those of man-made systems. Although understanding the chemical make-up of these systems is essential, the passive and active mechanics within biological systems are crucial when considering the many nat...
journal_title:Nature communications
pub_type: 杂志文章,评审
doi:10.1038/ncomms8418
更新日期:2015-07-06 00:00:00
abstract::Programmed cell death protein-1 (PD-1)/programmed cell death ligand-1 (PD-L1) interaction plays a crucial role in tumor-associated immune escape. Here, we verify that triple-negative breast cancer (TNBC) has higher PD-L1 expression than other subtypes. We then discover that nucleophosmin (NPM1) binds to PD-L1 promoter...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-020-15364-z
更新日期:2020-04-03 00:00:00
abstract::Acoustical tweezers open major prospects in microbiology for cells and microorganisms contactless manipulation, organization and mechanical properties testing since they are biocompatible, label-free and have the potential to exert forces several orders of magnitude larger than their optical counterpart at equivalent ...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-020-18000-y
更新日期:2020-08-25 00:00:00
abstract::Clostridium difficile is the leading cause of pseudomembranous colitis in hospitalized patients. C. difficile enterotoxins TcdA and TcdB promote this inflammatory condition via a cytotoxic response on intestinal epithelial cells (IECs), but the underlying mechanisms are incompletely understood. Additionally, TcdA and ...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-018-07386-5
更新日期:2018-11-19 00:00:00
abstract::The naked mole-rat (NMR, Heterocephalus glaber), which is the longest-lived rodent species, exhibits extraordinary resistance to cancer. Here we report that NMR somatic cells exhibit a unique tumour-suppressor response to reprogramming induction. In this study, we generate NMR-induced pluripotent stem cells (NMR-iPSCs...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms11471
更新日期:2016-05-10 00:00:00
abstract::A collective order of spin and charge degrees of freedom into stripes has been predicted to be a possible ground state of hole-doped CuO(2) planes, which are the building blocks of high-temperature superconductors. In fact, stripe-like spin and charge order has been observed in various layered cuprate systems. For the...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms2019
更新日期:2012-01-01 00:00:00
abstract::Selective reduction of ketone/aldehydes to alcohols is of great importance in green chemistry and chemical engineering. Highly efficient catalysts are still demanded to work under mild conditions, especially at room temperature. Here we present a synergistic function of single-atom palladium (Pd1) and nanoparticles (P...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-019-13941-5
更新日期:2020-01-07 00:00:00
abstract::Carbon-carbon bond forming reactions are essential transformations in natural product biosynthesis. During de novo fatty acid and polyketide biosynthesis, β-ketoacyl-acyl carrier protein (ACP) synthases (KS), catalyze this process via a decarboxylative Claisen-like condensation reaction. KSs must recognize multiple ch...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-020-15455-x
更新日期:2020-04-07 00:00:00
abstract::Transition metal oxides host a wealth of exotic phenomena ranging from charge, orbital and magnetic order to nontrivial topological phases and superconductivity. In order to translate these unique materials properties into device functionalities these materials must be doped; however, the nature of carriers and their ...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms15769
更新日期:2017-06-08 00:00:00
abstract::Type I interferon (IFN) is a key driver of immunity to infections and cancer. Plasmacytoid dendritic cells (pDCs) are uniquely equipped to produce large quantities of type I IFN but the mechanisms that control this process are poorly understood. Here we report on a droplet-based microfluidic platform to investigate ty...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-018-05784-3
更新日期:2018-08-20 00:00:00
abstract::Lithium- and sodium-rich layered transition-metal oxides have recently been attracting significant interest because of their large capacity achieved by additional oxygen-redox reactions. However, layered transition-metal oxides exhibit structural degradation such as cation migration, layer exfoliation or cracks upon d...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-019-09409-1
更新日期:2019-05-16 00:00:00
abstract::The turnover of messenger RNAs (mRNAs) is a key regulatory step of gene expression in eukaryotic cells. Due to the complexity of the mammalian degradation machinery, the contribution of decay factors to the directionality of mRNA decay is poorly understood. Here we characterize a molecular tool to interrogate mRNA tur...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms13691
更新日期:2016-12-05 00:00:00
abstract::Cellular protein-RNA complexes assemble on nascent transcripts, but methods to observe transcription and protein binding in real time and at physiological concentrations are not available. Here, we report a single-molecule approach based on zero-mode waveguides that simultaneously tracks transcription progress and the...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-018-07423-3
更新日期:2018-11-30 00:00:00
abstract::The mammary gland experiences substantial remodeling and regeneration during development and reproductive life, facilitated by stem cells and progenitors that act in concert with physiological stimuli. While studies have focused on deciphering regenerative cells within the parenchymal epithelium, cell lineages in the ...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-019-09748-z
更新日期:2019-04-15 00:00:00
abstract::Methane cold seep systems typically exhibit extensive buildups of authigenic carbonate minerals, resulting from local increases in alkalinity driven by methane oxidation. Here, we demonstrate that modern seep authigenic carbonates exhibit anomalously low clumped isotope values (Δ47), as much as ∼0.2‰ lower than expect...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms12274
更新日期:2016-07-22 00:00:00
abstract::Charge-to-spin conversion in various materials is the key for the fundamental understanding of spin-orbitronics and efficient magnetization manipulation. Here we report the direct spatial imaging of current-induced spin accumulation at the channel edges of Bi2Se3 and BiSbTeSe2 topological insulators as well as Pt by a...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-018-04939-6
更新日期:2018-06-27 00:00:00