57 research outputs found
Gate-tunable Topological Valley Transport in Bilayer Graphene
Valley pseudospin, the quantum degree of freedom characterizing the
degenerate valleys in energy bands, is a distinct feature of two-dimensional
Dirac materials. Similar to spin, the valley pseudospin is spanned by a time
reversal pair of states, though the two valley pseudospin states transform to
each other under spatial inversion. The breaking of inversion symmetry induces
various valley-contrasted physical properties; for instance, valley-dependent
topological transport is of both scientific and technological interests.
Bilayer graphene (BLG) is a unique system whose intrinsic inversion symmetry
can be controllably broken by a perpendicular electric field, offering a rare
possibility for continuously tunable valley-topological transport. Here, we
used a perpendicular gate electric field to break the inversion symmetry in
BLG, and a giant nonlocal response was observed as a result of the topological
transport of the valley pseudospin. We further showed that the valley transport
is fully tunable by external gates, and that the nonlocal signal persists up to
room temperature and over long distances. These observations challenge
contemporary understanding of topological transport in a gapped system, and the
robust topological transport may lead to future valleytronic applications
Copy number variations in 119 Chinese children with idiopathic short stature identified by the custom genome-wide microarray
Crystal Structure of the Receptor-Binding Domain of Botulinum Neurotoxin Type HA, Also Known as Type FA or H
Botulinum neurotoxins (BoNTs), which have been exploited as cosmetics and muscle-disorder treatment medicines for decades, are well known for their extreme neurotoxicity to humans. They pose a potential bioterrorism threat because they cause botulism, a flaccid muscular paralysis-associated disease that requires immediate antitoxin treatment and intensive care over a long period of time. In addition to the existing seven established BoNT serotypes (BoNT/A–G), a new mosaic toxin type termed BoNT/HA (aka type FA or H) was reported recently. Sequence analyses indicate that the receptor-binding domain (HC) of BoNT/HA is ~84% identical to that of BoNT/A1. However, BoNT/HA responds differently to some potent BoNT/A-neutralizing antibodies (e.g., CR2) that target the HC. Therefore, it raises a serious concern as to whether BoNT/HA poses a new threat to our biosecurity. In this study, we report the first high-resolution crystal structure of BoNT/HA-HC at 1.8 Å. Sequence and structure analyses reveal that BoNT/HA and BoNT/A1 are different regarding their binding to cell-surface receptors including both polysialoganglioside (PSG) and synaptic vesicle glycoprotein 2 (SV2). Furthermore, the new structure also provides explanations for the ~540-fold decreased affinity of antibody CR2 towards BoNT/HA compared to BoNT/A1. Taken together, these new findings advance our understanding of the structure and function of this newly identified toxin at the molecular level, and pave the way for the future development of more effective countermeasures
Crystal Structure of the Receptor-Binding Domain of Botulinum Neurotoxin Type HA, Also Known as Type FA or H.
N-linked glycosylation of SV2 is required for binding and uptake of botulinum neurotoxin A
A camelid single-domain antibody neutralizes botulinum neurotoxin A by blocking host receptor binding
Diverse binding modes, same goal: The receptor recognition mechanism of botulinum neurotoxin.
Botulinum neurotoxins (BoNTs) are among the most deadly toxins known. They act rapidly in a highly specific manner to block neurotransmitter release by cleaving the soluble N-ethylmaleimide sensitive factor attachment protein receptor (SNARE) complex at neuromuscular junctions. The extreme toxicity of BoNTs relies predominantly on their neurotropism that is accomplished by recognition of two host receptors, a polysialo-ganglioside and in the majority of cases a synaptic vesicle protein, through their receptor-binding domains. Two proteins, synaptotagmin and synaptic vesicle glycoprotein 2, have been identified as the receptors for various serotypes of BoNTs. Here, we review recent breakthroughs in the structural studies of BoNT-protein receptor recognitions that highlight a range of diverse mechanisms by which BoNTs manipulate host neuronal proteins for highly specific uptake at neuromuscular junctions
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Diverse binding modes, same goal: The receptor recognition mechanism of botulinum neurotoxin.
Botulinum neurotoxins (BoNTs) are among the most deadly toxins known. They act rapidly in a highly specific manner to block neurotransmitter release by cleaving the soluble N-ethylmaleimide sensitive factor attachment protein receptor (SNARE) complex at neuromuscular junctions. The extreme toxicity of BoNTs relies predominantly on their neurotropism that is accomplished by recognition of two host receptors, a polysialo-ganglioside and in the majority of cases a synaptic vesicle protein, through their receptor-binding domains. Two proteins, synaptotagmin and synaptic vesicle glycoprotein 2, have been identified as the receptors for various serotypes of BoNTs. Here, we review recent breakthroughs in the structural studies of BoNT-protein receptor recognitions that highlight a range of diverse mechanisms by which BoNTs manipulate host neuronal proteins for highly specific uptake at neuromuscular junctions
Botulinum Neurotoxin A Complex Recognizes Host Carbohydrates through Its Hemagglutinin Component
Botulinum neurotoxins (BoNTs) are potent bacterial toxins. The high oral toxicity of BoNTs is largely attributed to the progenitor toxin complex (PTC), which is assembled from BoNT and nontoxic neurotoxin-associated proteins (NAPs) that are produced together with BoNT in bacteria. Here, we performed ex vivo studies to examine binding of the highly homogeneous recombinant NAPs to mouse small intestine. We also carried out the first comprehensive glycan array screening with the hemagglutinin (HA) component of NAPs. Our data confirmed that intestinal binding of the PTC is partly mediated by the HA moiety through multivalent interactions between HA and host carbohydrates. The specific HA-carbohydrate recognition could be inhibited by receptor-mimicking saccharides
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