Abstract:
:To achieve global elimination of hepatitis C virus (HCV), an effective cross-genotype vaccine is needed. The HCV envelope glycoprotein E2 is the main target for neutralizing antibodies (nAbs), which aid in HCV clearance and protection. E2 is structurally flexible and functions in engaging host receptors. Many nAbs bind to the "neutralizing face" on E2, including several broadly nAbs encoded by the VH1-69 germline gene family that bind to a similar conformation (A) of this face. Here, a previously unknown conformation (B) of the neutralizing face is revealed in crystal structures of two of four additional E2-VH1-69 nAb complexes. In this conformation, the E2 front-layer region is displaced upon antibody binding, exposing residues in the back layer for direct antibody interaction. This E2 B structure may represent another conformational state in the viral entry process that is susceptible to antibody neutralization and thus provide a new target for rational vaccine development.
journal_name
Sci Advjournal_title
Science advancesauthors
Tzarum N,Giang E,Kadam RU,Chen F,Nagy K,Augestad EH,Velázquez-Moctezuma R,Keck ZY,Hua Y,Stanfield RL,Dreux M,Prentoe J,Foung SKH,Bukh J,Wilson IA,Law Mdoi
10.1126/sciadv.abb5642subject
Has Abstractpub_date
2020-07-24 00:00:00pages
eabb5642issue
30issn
2375-2548pii
abb5642journal_volume
6pub_type
杂志文章相关文献
Science Advances文献大全abstract::Immotile cilia sense extracellular signals such as fluid flow, but whether Ca2+ plays a role in flow sensing has been unclear. Here, we examined the role of ciliary Ca2+ in the flow sensing that initiates the breaking of left-right (L-R) symmetry in the mouse embryo. Intraciliary and cytoplasmic Ca2+ transients were d...
journal_title:Science advances
pub_type: 杂志文章
doi:10.1126/sciadv.aba1195
更新日期:2020-07-22 00:00:00
abstract::Carbon taxes are widely regarded as a potentially effective and economically efficient policy instrument for decarbonizing the global energy supply and thus limiting global warming. The main obstacle is political feasibility because of opposition from citizens and industry. Earmarking revenues from carbon taxation for...
journal_title:Science advances
pub_type: 杂志文章
doi:10.1126/sciadv.aax3323
更新日期:2019-09-18 00:00:00
abstract::Energy band engineering is of fundamental importance in nanoelectronics. Compared to chemical approaches such as doping and surface functionalization, electrical and optical methods provide greater flexibility that enables continuous, reversible, and in situ band tuning on electronic devices of various kinds. In this ...
journal_title:Science advances
pub_type: 杂志文章
doi:10.1126/sciadv.aav3430
更新日期:2019-05-03 00:00:00
abstract::Transcription factors control gene expression in all life. This raises the question of what is the smallest protein that can support such activity. In nature, Cro from bacteriophage λ is one of the smallest known repressors (66 amino acids), and activators are typically much larger (e.g., λ cI, 237 amino acids). Previ...
journal_title:Science advances
pub_type: 杂志文章
doi:10.1126/sciadv.aba2728
更新日期:2020-06-10 00:00:00
abstract::Adoptive cell transfers have emerged as a disruptive approach to treat disease in a manner that is more specific than using small-molecule drugs; however, unlike traditional drugs, cells are living entities that can alter their function in response to environmental cues. In the present study, we report an engineered p...
journal_title:Science advances
pub_type: 杂志文章
doi:10.1126/sciadv.aaz6579
更新日期:2020-04-29 00:00:00
abstract::The response to programmed cell death protein-1 (PD-1)/programmed death ligand-1 (PD-L1) blockade in cancer immunotherapy is limited because of multiple immune evasion mechanisms. Here, a previously unknown strategy is proposed to synergize the nuclear factor κB (NF-κB) inhibition and PD-1 blockade for antitumor immun...
journal_title:Science advances
pub_type: 杂志文章
doi:10.1126/sciadv.aay7785
更新日期:2020-02-05 00:00:00
abstract::Stroke is the most common cause of adult disability in developed countries, largely because spontaneous recovery is often incomplete, and no pharmacological means to hasten the recovery exist. It was recently shown that mesencephalic astrocyte-derived neurotrophic factor (MANF) induces alternative or M2 activation of ...
journal_title:Science advances
pub_type: 杂志文章
doi:10.1126/sciadv.aap8957
更新日期:2018-05-23 00:00:00
abstract::Fluctuations in biodiversity, large and small, pervade the fossil record, yet we do not understand the processes generating them. Here, we extend theory from nonequilibrium statistical physics to describe the fat-tailed form of fluctuations in Phanerozoic marine invertebrate richness. Using this theory, known as super...
journal_title:Science advances
pub_type: 杂志文章
doi:10.1126/sciadv.aat0122
更新日期:2019-06-26 00:00:00
abstract::Photoresponsive liquid crystalline elastomers (LCEs) constitute ideal actuators for soft robots because their light-induced macroscopic shape changes can be harnessed to perform specific articulated motions. Conventional LCEs, however, do not typically exhibit complex modes of bending and twisting necessary to perform...
journal_title:Science advances
pub_type: 杂志文章
doi:10.1126/sciadv.aay5349
更新日期:2020-03-27 00:00:00
abstract::Spin caloritronics has recently emerged from the combination of spintronics and thermoelectricity. Here, we show that flexible, macroscopic spin caloritronic devices based on large-area interconnected magnetic nanowire networks can be used to enable controlled Peltier cooling of macroscopic electronic components with ...
journal_title:Science advances
pub_type: 杂志文章
doi:10.1126/sciadv.aav2782
更新日期:2019-03-01 00:00:00
abstract::This study introduces new methods of screening for and tuning chiral space and in so doing identifies a promising set of chiral ligands for asymmetric synthesis. The carbafructopyranosyl-1,2-diamine(s) and salens constructed therefrom are particularly compelling. It is shown that by removing the native anomeric effect...
journal_title:Science advances
pub_type: 杂志文章
doi:10.1126/sciadv.1500066
更新日期:2015-07-01 00:00:00
abstract::The tetrapod neuronal protein ARC and its Drosophila melanogaster homolog, dARC1, have important but differing roles in neuronal development. Both are thought to originate through exaptation of ancient Ty3/Gypsy retrotransposon Gag, with their novel function relying on an original capacity for self-assembly and encaps...
journal_title:Science advances
pub_type: 杂志文章
doi:10.1126/sciadv.aay6354
更新日期:2020-01-01 00:00:00
abstract::Mesoscale turbulence in the ocean strongly affects the circulation, water mass formation, and transport of tracers. Little is known, however, about how mixing varies on climate timescales. We present the first time-resolved global dataset of lateral mesoscale eddy diffusivities at the ocean surface, obtained by applyi...
journal_title:Science advances
pub_type: 杂志文章
doi:10.1126/sciadv.aav5014
更新日期:2019-01-23 00:00:00
abstract::Microsupercapacitors (MSCs) have garnered considerable attention as a promising power source for microelectronics and miniaturized portable/wearable devices. However, their practical application has been hindered by the manufacturing complexity and dimensional limits. Here, we develop a new class of ultrahigh areal nu...
journal_title:Science advances
pub_type: 杂志文章
doi:10.1126/sciadv.aaz1692
更新日期:2020-03-06 00:00:00
abstract::Identifying key players in coupled individual systems is a fundamental problem in network theory. We investigate synchronizable network-coupled dynamical systems such as high-voltage electric power grids and coupled oscillators on complex networks. We define key players as nodes that, once perturbed, generate the larg...
journal_title:Science advances
pub_type: 杂志文章
doi:10.1126/sciadv.aaw8359
更新日期:2019-11-22 00:00:00
abstract::Tumor angiogenesis provides critical nutrients for cancer progression and may also facilitate pathways for dissemination during the process of metastasis. It is well established that cells that metastasize display characteristics of stem cells; however, the prevailing paradigm points to these stem-like cells residing ...
journal_title:Science advances
pub_type: 杂志文章
doi:10.1126/sciadv.1701350
更新日期:2017-10-25 00:00:00
abstract::Nanometer-scale skyrmions are prospective candidates for information bits in low-power consumption devices owing to their topological nature and controllability with low current density. Studies on skyrmion dynamics in different classes of materials have exploited the topological Hall effect and current-driven fast mo...
journal_title:Science advances
pub_type: 杂志文章
doi:10.1126/sciadv.aaz9744
更新日期:2020-06-17 00:00:00
abstract::Mineralization is the most fundamental process in vertebrates. It is predominantly mediated by osteoblasts, which secrete mineral precursors, most likely through matrix vesicles (MVs). These vesicular structures are calcium and phosphate rich and contain organic material such as acidic proteins. However, it remains la...
journal_title:Science advances
pub_type: 杂志文章
doi:10.1126/sciadv.aax0672
更新日期:2019-07-03 00:00:00
abstract::Several forms of hair loss in humans are characterized by the inability of hair follicles to enter the growth phase (anagen) of the hair cycle after being arrested in the resting phase (telogen). Current pharmacologic therapies have been largely unsuccessful in targeting pathways that can be selectively modulated to i...
journal_title:Science advances
pub_type: 杂志文章
doi:10.1126/sciadv.1500973
更新日期:2015-10-23 00:00:00
abstract::Altered cerebral glucose uptake is one of the hallmarks of Alzheimer's disease (AD). A dynamic glucose-enhanced (DGE) magnetic resonance imaging (MRI) approach was developed to simultaneously monitor d-glucose uptake and clearance in both brain parenchyma and cerebrospinal fluid (CSF). We observed substantially higher...
journal_title:Science advances
pub_type: 杂志文章
doi:10.1126/sciadv.aba3884
更新日期:2020-05-13 00:00:00
abstract::Predicted changes in the intensity and frequency of climate extremes urge a better mechanistic understanding of the stress response of microbially mediated carbon (C) and nutrient cycling processes. We analyzed the resistance and resilience of microbial C, nitrogen (N), and phosphorus (P) cycling processes and microbi...
journal_title:Science advances
pub_type: 杂志文章
doi:10.1126/sciadv.1602781
更新日期:2017-05-03 00:00:00
abstract::The urea channel of Helicobacterpylori (HpUreI) is an ideal drug target for preventing gastric cancer but incomplete understanding of its gating mechanism has hampered development of inhibitors for the eradication of H. pylori. Here, we present the cryo-EM structures of HpUreI in closed and open conformations, both at...
journal_title:Science advances
pub_type: 杂志文章
doi:10.1126/sciadv.aav8423
更新日期:2019-03-20 00:00:00
abstract::Candida albicans is a pathogenic yeast that causes mucosal and systematic infections with high mortality. The absence of facile molecular genetics has been a major impediment to analysis of pathogenesis. The lack of meiosis coupled with the absence of plasmids makes genetic engineering cumbersome, especially for essen...
journal_title:Science advances
pub_type: 杂志文章
doi:10.1126/sciadv.1500248
更新日期:2015-01-01 00:00:00
abstract::The Late Paleogene surface height and paleoenvironment for the core area of the Qinghai-Tibetan Plateau (QTP) remain critically unresolved. Here, we report the discovery of the youngest well-preserved fossil palm leaves from Tibet. They were recovered from the Late Paleogene (Chattian), ca. 25.5 ± 0.5 million years, p...
journal_title:Science advances
pub_type: 杂志文章
doi:10.1126/sciadv.aav2189
更新日期:2019-03-06 00:00:00
abstract::Human and murine skin wounding commonly results in fibrotic scarring, but the murine wounding model wound-induced hair neogenesis (WIHN) can frequently result in a regenerative repair response. Here, we show in single-cell RNA sequencing comparisons of semi-regenerative and fibrotic WIHN wounds, increased expression o...
journal_title:Science advances
pub_type: 杂志文章
doi:10.1126/sciadv.aay3704
更新日期:2020-03-20 00:00:00
abstract::Several neurological disorders may benefit from gene therapy. However, even when using the lead vector candidate for intrathecal administration, adeno-associated virus serotype 9 (AAV9), the strength and distribution of gene transfer to the brain are inconsistent. On the basis of preliminary observations that standard...
journal_title:Science advances
pub_type: 杂志文章
doi:10.1126/sciadv.aau9859
更新日期:2018-11-14 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::Cytosolic RNA sensing is a prerequisite for initiation of innate immune response against RNA viral pathogens. Signaling through RIG-I (retinoic acid-inducible gene I)-like receptors (RLRs) to TBK1 (Tank-binding kinase 1)/IKKε (IκB kinase ε) kinases is transduced by mitochondria-associated MAVS (mitochondrial antiviral...
journal_title:Science advances
pub_type: 杂志文章
doi:10.1126/sciadv.1501889
更新日期:2016-07-01 00:00:00
abstract::Coherent interactions between electromagnetic and matter waves lie at the heart of quantum science and technology. However, the diffraction nature of light has limited the scalability of many atom-light-based quantum systems. We use the optical fields in a hollow-core photonic crystal fiber to spatially split, reflect...
journal_title:Science advances
pub_type: 杂志文章
doi:10.1126/sciadv.1701723
更新日期:2018-01-19 00:00:00
abstract::The first example of a homogeneous silver(I)-catalyzed aerobic oxidation of aldehydes in water is reported. More than 50 examples of different aliphatic and aromatic aldehydes, including natural products, were tested, and all of them successfully underwent aerobic oxidation to give the corresponding carboxylic acids i...
journal_title:Science advances
pub_type: 杂志文章
doi:10.1126/sciadv.1500020
更新日期:2015-03-27 00:00:00