93 research outputs found
Botulinum Neurotoxin Devoid of Receptor Binding Domain Translocates Active Protease
Clostridium botulinum neurotoxin (BoNT) causes flaccid paralysis by disabling synaptic exocytosis. Intoxication requires the tri-modular protein to undergo conformational changes in response to pH and redox gradients across endosomes, leading to the formation of a protein-conducting channel. The ∼50 kDa light chain (LC) protease is translocated into the cytosol by the ∼100 kDa heavy chain (HC), which consists of two modules: the N-terminal translocation domain (TD) and the C-terminal Receptor Binding Domain (RBD). Here we exploited the BoNT modular design to identify the minimal requirements for channel activity and LC translocation in neurons. Using the combined detection of substrate proteolysis and single-channel currents, we showed that a di-modular protein consisting only of LC and TD was sufficient to translocate active protease into the cytosol of target cells. The RBD is dispensable for cell entry, channel activity, or LC translocation; however, it determined a pH threshold for channel formation. These findings indicate that, in addition to its individual functions, each module acts as a chaperone for the others, working in concert to achieve productive intoxication
Polymer solution and lattice theory applications for modeling of asphaltene precipitation in petroleum mixtures
Vibrational spectroscopic, NMR parameters and electronic properties of three 3-phenylthiophene derivatives via density functional theory
NITROGEN COMPOUND DISTRIBUTION AND FUEL INCOMPATIBILITY REACTIONS IN A TAR SAND DERIVED MIDDLE DISTILLATE FUEL
Lubricity-Enhancing Properties of Soy Oil When Used as a Blending Stock for Middle Distillate Fuels
CHEMICAL BASIS OF MIDDLE DISTILLATE FUEL INSTABILITY: Interactive Effects of Selected Nitrogen Heterocycles with Organic Bases in a Shale-Derived Diesel Fuel.
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