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Sialylation of immunoglobulin E is a determinant of allergic pathogenicity
Approximately one-third of the world's population suffers from allergies1. Exposure to allergens crosslinks immunoglobulin E (IgE) antibodies that are bound to mast cells and basophils, triggering the release of inflammatory mediators, including histamine2. Although IgE is absolutely required for allergies, it is not understood why total and allergen-specific IgE concentrations…
View PublicationClustering of human prion protein and α-synuclein oligomers requires the prion protein N-terminus
The interaction of prion protein (PrP) and α-synuclein (αSyn) oligomers causes synaptic impairment that might trigger Parkinson’s disease and other synucleinopathies. Here, we report that αSyn oligomers (αSynO) cluster with human PrP (huPrP) into micron-sized condensates. Multivalency of αSyn within oligomers is required for condensation, since clustering with huPrP is…
View PublicationIncreased surface charge in the protein chaperone Spy enhances its anti-aggregation activity
Chaperones are essential components of the protein homeostasis network. There is a growing interest in optimizing chaperone function, but exactly how to achieve this aim is unclear. Here, using a model chaperone, the bacterial protein Spy, we demonstrate that substitutions that alter the electrostatic potential of Spy's concave, client-binding surface…
View PublicationCancer-associated fibroblasts-derived VCAM1 induced by H. pylori infection facilitates tumor invasion in gastric cancer
Cancer-associated fibroblasts (CAFs) play a major role in the progression of stomach cancer, but the related mechanisms are not fully understood. H. pylori infection is recognized as one of the strongest risk factors for gastric carcinoma, but its effects on CAFs remain unknown. We aimed to determine the causative relationship…
View PublicationComprehensive survey of the VxGΦL motif of PP2Cs from Oryza sativa reveals the critical role of the fourth position in regulation of ABA responsiveness
Regulation of abscisic acid (ABA) signaling is crucial in balancing responses to abiotic stresses and retaining growth in planta. An ABA receptor (PYL/RCAR) and a protein phosphatase (PP2C), a co-receptor, form a complex upon binding to ABA. Previously we reported that the second and fourth positions in the VxGΦL motif…
View PublicationStructural basis for chain release from the enacyloxin polyketide synthase
Modular polyketide synthases and non-ribosomal peptide synthetases are molecular assembly lines that consist of several multienzyme subunits that undergo dynamic self-assembly to form a functional megacomplex. N- and C-terminal docking domains are usually responsible for mediating the interactions between subunits. Here we show that communication between two non-ribosomal peptide synthetase…
View PublicationFcRn overexpression in human cancer drives albumin recycling and cell growth; a mechanistic basis for exploitation in targeted albumin-drug designs
Albumin accumulation in tumours could reflect a role of albumin in transport of endogenous nutrient cargos required for cellular growth and not just a suggested source of amino acids; a role driven by albumin engagement with its cognate cellular recycling neonatal Fc receptor. We investigate the hypothesis that albumin cellular…
View PublicationNAD+ biosynthesis in bacteria is controlled by global carbon/nitrogen levels via PII signaling
NAD+ is a central metabolite participating in core metabolic redox reactions. The prokaryotic NAD synthetase enzyme NadE catalyzes the last step of NAD+ biosynthesis, converting nicotinic acid adenine dinucleotide (NaAD) to NAD+ Some members of the NadE family use l-glutamine as a nitrogen donor and are named NadEGln Previous gene…
View PublicationStructure of the Peptidoglycan Synthase Activator LpoP in Pseudomonas aeruginosa
Peptidoglycan (PG) is an essential component of the bacterial cell wall and is assembled from a lipid II precursor by glycosyltransferase and transpeptidase reactions catalyzed in particular by bifunctional class A penicillin-binding proteins (aPBPs). In the major clinical pathogen Pseudomonas aeruginosa, PBP1B is anchored within the cytoplasmic membrane but regulated…
View PublicationFc-Based Recombinant Henipavirus Vaccines Elicit Broad Neutralizing Antibody Responses in Mice
The genus Henipavirus (HNVs) includes two fatal viruses, namely Nipah virus (NiV) and Hendra virus (HeV). Since 1994, NiV and HeV have been endemic to the Asia–Pacific region and responsible for more than 600 cases of infections. Two emerging HNVs, Ghana virus (GhV) and Mojiang virus (MojV), are speculated to be associated…
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