Abstract:
:Cholesterol-dependent cytolysins (CDCs) form pores in cholesterol-rich membranes, but cholesterol alone is insufficient to explain their cell and host tropism. Here, we show that all eight major CDCs have high-affinity lectin activity that identifies glycans as candidate cellular receptors. Streptolysin O, vaginolysin, and perfringolysin O bind multiple glycans, while pneumolysin, lectinolysin, and listeriolysin O recognize a single glycan class. Addition of exogenous carbohydrate receptors for each CDC inhibits toxin activity. We present a structure for suilysin domain 4 in complex with two distinct glycan receptors, P1 antigen and αGal/Galili. We report a wide range of binding affinities for cholesterol and for the cholesterol analog pregnenolone sulfate and show that CDCs bind glycans and cholesterol independently. Intermedilysin binds to the sialyl-TF O-glycan on its erythrocyte receptor, CD59. Removing sialyl-TF from CD59 reduces intermedilysin binding. Glycan-lectin interactions underpin the cellular tropism of CDCs and provide molecular targets to block their cytotoxic activity.
journal_name
Sci Advjournal_title
Science advancesauthors
Shewell LK,Day CJ,Jen FE,Haselhorst T,Atack JM,Reijneveld JF,Everest-Dass A,James DBA,Boguslawski KM,Brouwer S,Gillen CM,Luo Z,Kobe B,Nizet V,von Itzstein M,Walker MJ,Paton AW,Paton JC,Torres VJ,Jennings MPdoi
10.1126/sciadv.aaz4926subject
Has Abstractpub_date
2020-05-22 00:00:00pages
eaaz4926issue
21issn
2375-2548pii
aaz4926journal_volume
6pub_type
杂志文章相关文献
Science Advances文献大全abstract::Electrochemical analysis of sweat using soft bioelectronics on human skin provides a new route for noninvasive glucose monitoring without painful blood collection. However, sweat-based glucose sensing still faces many challenges, such as difficulty in sweat collection, activity variation of glucose oxidase due to lact...
journal_title:Science advances
pub_type: 杂志文章
doi:10.1126/sciadv.1601314
更新日期:2017-03-08 00:00:00
abstract::Fluid commonly flows in response to an external pressure gradient. However, when a tunnel-containing hydrogel is immersed in water, spontaneous flow occurs through the tunnel without any pressure gradient. We confirmed this flow in a wide range of plant- and animal-derived hydrogels. The flow appears to be driven by a...
journal_title:Science advances
pub_type: 杂志文章
doi:10.1126/sciadv.aba0941
更新日期:2020-05-08 00:00:00
abstract::G-quadruplex (G4) is one of the most important secondary structures in nucleic acids. Until recently, G4 RNAs have not been reported in any ribovirus, such as the hepatitis C virus. Our bioinformatics analysis reveals highly conserved guanine-rich consensus sequences within the core gene of hepatitis C despite the hig...
journal_title:Science advances
pub_type: 杂志文章
doi:10.1126/sciadv.1501535
更新日期:2016-04-01 00:00:00
abstract::Demonstration of ultralow energy switching mechanisms is imperative for continued improvements in computing devices. Ferroelectric (FE) and multiferroic (MF) order and their manipulation promise an ideal combination of state variables to reach attojoule range for logic and memory (i.e., ~30× lower switching energy tha...
journal_title:Science advances
pub_type: 杂志文章
doi:10.1126/sciadv.aat4229
更新日期:2018-11-23 00:00:00
abstract::Many applications in modern technology, such as self-cleaning surfaces and digital microfluidics, require control over individual fluid droplets on flat surfaces. Existing techniques may suffer from side effects resulting from high electric fields and high temperatures. Here, we introduce a markedly different method, ...
journal_title:Science advances
pub_type: 杂志文章
doi:10.1126/sciadv.aaw0914
更新日期:2019-06-14 00:00:00
abstract::Many animals understand numbers at a basic level for use in essential tasks such as foraging, shoaling, and resource management. However, complex arithmetic operations, such as addition and subtraction, using symbols and/or labeling have only been demonstrated in a limited number of nonhuman vertebrates. We show that ...
journal_title:Science advances
pub_type: 杂志文章
doi:10.1126/sciadv.aav0961
更新日期:2019-02-06 00:00:00
abstract::Iron deficiency and anemia are prominent contributors to the preventable disease burden worldwide. A substantial proportion of people with inadequate dietary iron rely on rice as a staple food, but fortification efforts are limited by low iron bioavailability. Furthermore, using high iron fortification dosages may not...
journal_title:Science advances
pub_type: 杂志文章
doi:10.1126/sciadv.aau0790
更新日期:2019-03-27 00:00:00
abstract::The structure of many real-world systems is best captured by networks consisting of several interaction layers. Understanding how a multilayered structure of connections affects the synchronization properties of dynamical systems evolving on top of it is a highly relevant endeavor in mathematics and physics and has po...
journal_title:Science advances
pub_type: 杂志文章
doi:10.1126/sciadv.1601679
更新日期:2016-11-16 00:00:00
abstract::Optogenetics is a paradigm-changing new method to study and manipulate the behavior of cells with light. Following major advances of the used genetic constructs over the last decade, the light sources required for optogenetic control are now receiving increased attention. We report a novel optogenetic illumination pla...
journal_title:Science advances
pub_type: 杂志文章
doi:10.1126/sciadv.1600061
更新日期:2016-05-06 00:00:00
abstract::Transistors with exfoliated two-dimensional (2D) materials on a SiO2/Si substrate have been applied and have been proven effective in a wide range of applications, such as circuits, memory, photodetectors, gas sensors, optical modulators, valleytronics, and spintronics. However, these devices usually suffer from limit...
journal_title:Science advances
pub_type: 杂志文章
doi:10.1126/sciadv.1602246
更新日期:2017-05-19 00:00:00
abstract::The ongoing conservation treatment program of the Ghent Altarpiece by Hubert and Jan Van Eyck, one of the iconic paintings of the west, has revealed that the designs of the paintings were changed several times, first by the original artists, and then during later restorations. The central motif, The Lamb of God, repre...
journal_title:Science advances
pub_type: 杂志文章
doi:10.1126/sciadv.abb3379
更新日期:2020-07-29 00:00:00
abstract::Leukemia is a complex heterogeneous disease often driven by the expression of oncogenic fusion proteins with different molecular and biochemical properties. Whereas several fusion proteins induce leukemogenesis by activating Hox gene expression (Hox-activating fusions), others impinge on different pathways that do not...
journal_title:Science advances
pub_type: 杂志文章
doi:10.1126/sciadv.1600972
更新日期:2016-10-07 00:00:00
abstract::Nanomaterials often surprise us with unexpected phenomena. Here, we report a discovery of the anti-twinning deformation, previously thought impossible, in nanoscale body-centered cubic (BCC) tungsten crystals. By conducting in situ transmission electron microscopy nanomechanical testing, we observed the nucleation and...
journal_title:Science advances
pub_type: 杂志文章
doi:10.1126/sciadv.aay2792
更新日期:2020-06-03 00:00:00
abstract::The cellular and the molecular mechanisms by which long noncoding RNAs (lncRNAs) may regulate presynaptic function and neuronal activity are largely unexplored. Here, we established an integrated screening strategy to discover lncRNAs implicated in neurotransmitter and synaptic vesicle release. With this approach, we ...
journal_title:Science advances
pub_type: 杂志文章
doi:10.1126/sciadv.aay2670
更新日期:2019-12-18 00:00:00
abstract::The lipid bilayer membrane, which is the foundation of life on Earth, is not viable outside of biology based on liquid water. This fact has caused astronomers who seek conditions suitable for life to search for exoplanets within the "habitable zone," the narrow band in which liquid water can exist. However, can cell m...
journal_title:Science advances
pub_type: 杂志文章
doi:10.1126/sciadv.1400067
更新日期:2015-02-27 00:00:00
abstract::Using a national longitudinal survey data set from the Higher Education Research Institute, this study tested whether students who identified as a sexual minority (for example, lesbian, gay, bisexual, or queer) were more or less likely to persist after 4 years in science, technology, engineering, and mathematics (STEM...
journal_title:Science advances
pub_type: 杂志文章
doi:10.1126/sciadv.aao6373
更新日期:2018-03-14 00:00:00
abstract::The established model-free methods for the processing of two-electron dipolar spectroscopy data [DEER (double electron-electron resonance), PELDOR (pulsed electron double resonance), DQ-EPR (double-quantum electron paramagnetic resonance), RIDME (relaxation-induced dipolar modulation enhancement), etc.] use regularize...
journal_title:Science advances
pub_type: 杂志文章
doi:10.1126/sciadv.aat5218
更新日期:2018-08-24 00:00:00
abstract::Annexin-A1 (ANXA1) has recently been proposed to play a role in microglial activation after brain ischemia, but the underlying mechanism remains poorly understood. Here, we demonstrated that ANXA1 is modified by SUMOylation, and SUMOylated ANXA1 could promote the beneficial phenotype polarization of microglia. Mechani...
journal_title:Science advances
pub_type: 杂志文章
doi:10.1126/sciadv.abc5539
更新日期:2021-01-20 00:00:00
abstract::Bioengineered three-dimensional (3D) matrices expand our experimental repertoire to study tumor growth and progression in a biologically relevant, yet controlled, manner. Here, we used peptide amphiphiles (PAs) to coassemble with and organize extracellular matrix (ECM) proteins producing tunable 3D models of the tumor...
journal_title:Science advances
pub_type: 杂志文章
doi:10.1126/sciadv.abb3298
更新日期:2020-10-02 00:00:00
abstract::The cyclic GMP-AMP synthase (cGAS), a sensor of cytosolic DNA, is critical for the innate immune response. Here, we show that loss of cGAS in untransformed and cancer cells results in uncontrolled DNA replication, hyperproliferation, and genomic instability. While the majority of cGAS is cytoplasmic, a fraction of cGA...
journal_title:Science advances
pub_type: 杂志文章
doi:10.1126/sciadv.abb8941
更新日期:2020-10-14 00:00:00
abstract::High-entropy alloys exhibit exceptional mechanical properties at cryogenic temperatures, due to the activation of twinning in addition to dislocation slip. The coexistence of multiple deformation pathways raises an important question regarding how individual deformation mechanisms compete or synergize during plastic d...
journal_title:Science advances
pub_type: 杂志文章
doi:10.1126/sciadv.aax4002
更新日期:2020-03-27 00:00:00
abstract::Cell chirality is a newly discovered intrinsic property of the cell, reflecting the bias of the cell to polarize in the left-right axis. Despite increasing evidence on its substantial role in the asymmetric development of embryos, little is known about implications of cell chirality in physiology and disease. We demon...
journal_title:Science advances
pub_type: 杂志文章
doi:10.1126/sciadv.aat2111
更新日期:2018-10-24 00:00:00
abstract::The importance of comets for the origin of life on Earth has been advocated for many decades. Amino acids are key ingredients in chemistry, leading to life as we know it. Many primitive meteorites contain amino acids, and it is generally believed that these are formed by aqueous alterations. In the collector aerogel a...
journal_title:Science advances
pub_type: 杂志文章
doi:10.1126/sciadv.1600285
更新日期:2016-05-27 00:00:00
abstract::Poor transport of neuropharmaceutics through central nervous system (CNS) barriers limits the development of effective treatments for CNS disorders. We present the facile synthesis of a novel neuroinflammation-targeting polyethylene glycol-based dendrimer (PEGOL-60) using an efficient click chemistry approach. PEGOL-6...
journal_title:Science advances
pub_type: 杂志文章
doi:10.1126/sciadv.aay8514
更新日期:2020-01-22 00:00:00
abstract::Peptidyl arginine deiminase 4 (PAD4) is a nuclear enzyme that converts arginine residues to citrulline. Although increasingly implicated in inflammatory disease and cancer, the mechanism of action of PAD4 and its functionally relevant pathways remains unclear. E2F transcription factors are a family of master regulator...
journal_title:Science advances
pub_type: 杂志文章
doi:10.1126/sciadv.1501257
更新日期:2016-02-05 00:00:00
abstract::A key problem in the study of the senses is to describe how sense organs extract perceptual information from the physics of the environment. We previously observed that dynamic touch elicits mechanical waves that propagate throughout the hand. Here, we show that these waves produce an efficient encoding of tactile inf...
journal_title:Science advances
pub_type: 杂志文章
doi:10.1126/sciadv.aaz1158
更新日期:2020-04-15 00:00:00
abstract::Porous materials, which are characterized by the large surface area and percolated nature crucial for transport, play an important role in many technological applications including battery, ion exchange, catalysis, microelectronics, medical diagnosis, and oil recovery. Phase separation of a mixture in such a porous st...
journal_title:Science advances
pub_type: 杂志文章
doi:10.1126/sciadv.aap9570
更新日期:2017-12-22 00:00:00
abstract::Species interactions have long been predicted to increase in intensity toward the tropics and low elevations because of gradients in climate, productivity, or biodiversity. Despite their importance for understanding global ecological and evolutionary processes, plant-animal interaction gradients are particularly diffi...
journal_title:Science advances
pub_type: 杂志文章
doi:10.1126/sciadv.aau4403
更新日期:2019-02-20 00:00:00
abstract::The accelerating global spread of arboviruses, such as Zika virus (ZIKV), highlights the need for more proactive mosquito surveillance. However, a major challenge during arbovirus outbreaks has been the lack of rapid and affordable tests for pathogen detection in mosquitoes. We show for the first time that near-infrar...
journal_title:Science advances
pub_type: 杂志文章
doi:10.1126/sciadv.aat0496
更新日期:2018-05-23 00:00:00
abstract::Plasmonic metasurfaces are a promising route for flat panel display applications due to their full color gamut and high spatial resolution. However, this plasmonic coloration cannot be readily tuned and requires expensive lithographic techniques. Here, we present scalable electrically driven color-changing metasurface...
journal_title:Science advances
pub_type: 杂志文章
doi:10.1126/sciadv.aaw2205
更新日期:2019-05-10 00:00:00