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News & Views |
A (cross)link in the chains
Interactions between proteins and non-proteinaceous biopolymers are essential for life; however, many methods used to characterize these interactions lack precision and display significant biases. Now, a genetically encoded method employing sulfur(vi) fluoride exchange (SuFEx)-based chemical crosslinking has been developed for capturing and analysing protein–RNA and protein–carbohydrate interactions in vivo.
- Christopher P. Watkins
- & Ryan A. Flynn
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Article |
A glycan gate controls opening of the SARS-CoV-2 spike protein
The opening mechanism of the SARS-CoV-2 spike protein has been studied by integrating computational and experimental data. Combining weighted ensemble molecular dynamics simulations, biolayer interferometry and ManifoldEM analysis of cryo-EM data revealed that the glycan at N343 plays a gating role in the opening mechanism of the SARS-CoV-2 spike protein.
- Terra Sztain
- , Surl-Hee Ahn
- & Rommie E. Amaro
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Article |
Synthetic O-acetylated sialosides facilitate functional receptor identification for human respiratory viruses
The specificity of human and animal viruses that engage with O-acetylated sialic acids has now been probed using a collection of O-acetylated sialoglycans obtained by diversification of trisaccharide precursors with viral haemagglutinin–esterases. The results revealed host-specific patterns of receptor recognition and showed that human respiratory viruses uniquely employ 9-O-acetylated α2,8-linked disialosides as receptors.
- Zeshi Li
- , Yifei Lang
- & Geert-Jan Boons
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Article |
O-GlcNAc modification of small heat shock proteins enhances their anti-amyloid chaperone activity
The post-translational modification O-GlcNAc on amyloid-forming proteins can inhibit their aggregation. Now, it has been shown that O-GlcNAc modification of small heat shock proteins HSP27, αA- and αB-crystallin can increase their anti-amyloid activity and block the amyloid formation of both α-synuclein and Aβ(1–42). A mechanism for this protective effect based on decreased physical interactions is also proposed.
- Aaron T. Balana
- , Paul M. Levine
- & Matthew R. Pratt
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News & Views |
Robots command enzymes
Enzymatic approaches to synthesize oligosaccharides offer an alternative to chemical syntheses for the production of homogeneous glycans; however, enzyme-based routes typically require lengthy processes. Now, the design of a water-soluble affinity tag has enabled the automation of multistep enzymatic syntheses of mammalian oligosaccharides.
- Nicola L. B. Pohl
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Article |
Streamlining the chemoenzymatic synthesis of complex N-glycans by a stop and go strategy
Preparation of well-defined N-glycans is very demanding, which hampers progress in glycoscience. Now, a biomimetic synthetic approach has been developed in which a readily available bi-antennary glycan can be converted in ten or fewer steps into multi-antennary N-glycans. This approach enables each arm to be uniquely extended by glycosyltransferases to give complex branched N-glycans.
- Lin Liu
- , Anthony R. Prudden
- & Geert-Jan Boons
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Article |
Chemical polyglycosylation and nanolitre detection enables single-molecule recapitulation of bacterial sugar export
Capsular polysaccharides are a protective layer enveloping pathogenic bacteria. Understanding their export could guide the design of therapeutics that render bacteria vulnerable to attack by the immune system or other therapeutic agents. Now, a synthetic strategy of polyglycosylation has been developed to obtain defined capsular polysaccharide fragments. Subsequent nanolitre detection enables their export to be studied at the single-molecule level.
- Lingbing Kong
- , Andrew Almond
- & Benjamin G. Davis
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News & Views |
A sweet vaccine
Vaccination with a synthetic glycoconjugate, in combination with the administration of an inhibitor that blocks capsular polysaccharide synthesis in bacteria, could offer an alternative route to combat bacterial infections.
- David Bundle
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Article |
An antibacterial vaccination strategy based on a glycoconjugate containing the core lipopolysaccharide tetrasaccharide Hep2Kdo2
The presence and linkage of unusual higher sugars in the ‘inner core’ of Gram-negative bacteria makes the core lipopolysacchride tetrasaccharide Hep2Kdo2 a tough target. Now, a 2+2 glycosylation strategy has facilitated the synthesis of this glycoconjugate. Synthesis of Hep2Kdo2 enabled an antibacterial vaccination strategy based on immunization with the glycoconjugate and the subsequent administration of an inhibitor that uncovers the corresponding epitope in pathogenic bacteria.
- Lingbing Kong
- , Balakumar Vijayakrishnan
- & Benjamin G. Davis
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Article |
O-GlcNAc modification blocks the aggregation and toxicity of the protein α-synuclein associated with Parkinson's disease
O-linked N-acetyl-glucosamine (O-GlcNAc) has been identified as an endogenous modification of α-synuclein; however, its effect on the properties of the protein is unclear. Now, recombinant protein and synthetic peptides have been combined to produce both unmodified and site-specifically O-GlcNAc-modified α-synuclein. The O-GlcNAc modification at threonine 72 was shown to inhibit the aggregation and associated toxicity of α-synuclein.
- Nicholas P. Marotta
- , Yu Hsuan Lin
- & Matthew R. Pratt