title: Receptor and substrate interactions of clostridial neurotoxins.
abstract: The high potency of clostridial neurotoxins relies predominantly on their neurospecific binding and specific hydrolysis of SNARE proteins. Their multi-step mode of mechanism can be ascribed to their multi-domain three-dimensional structure. The C-terminal H(CC)-domain interacts subsequently with complex polysialo-gangliosides such as GT1b and a synaptic vesicle protein receptor via two neighbouring binding sites, resulting in highly specific uptake of the neurotoxins at synapses of cholinergic motoneurons. After its translocation the enzymatically active light chain specifically hydrolyses specific SNARE proteins, preventing SNARE complex assembly and thereby blocking exocytosis of neurotransmitter.
authors.affiliation: The Howard Hughes Medical Institute and Departments of Molecular and Cellular Physiology, Neurology and Neurological Sciences, Structural Biology, and Photon Science, Stanford University, J.H. Clark Center, E300C, 318 Campus Drive, Stanford, CA 94305, USA. brunger@stanford.edu
authors.forename: Axel T
authors.initials: AT
authors.lastname: Brunger
authors.forename: Andreas
authors.initials: A
authors.lastname: Rummel
mesh_terms: D000818:Animals; D001905:Botulinum Toxins / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D002799:Cholinergic Fibers / Q000187:drug effects / Q000378:metabolism; D005732:Gangliosides / Q000378:metabolism*; D006801:Humans; D009046:Motor Neurons / Q000187:drug effects* / Q000378:metabolism; D009498:Neurotoxins / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D011485:Protein Binding; D050600:SNARE Proteins / Q000187:drug effects* / Q000378:metabolism; D013329:Structure-Activity Relationship; D013570:Synaptic Membranes / Q000187:drug effects / Q000378:metabolism; D050857:Synaptotagmins / Q000187:drug effects / Q000378:metabolism; D013744:Tetanus Toxin / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D005732:Gangliosides; D009498:Neurotoxins; D050600:SNARE Proteins; D013744:Tetanus Toxin; D050857:Synaptotagmins; D001905:Botulinum Toxins