Cocrystal structure of synaptobrevin-II bound to botulinum neurotoxin type B at 2.0 A resolution.
Botulinum neurotoxin serotype B is a zinc protease that disrupts neurotransmitter release by cleaving synaptobrevin-II (Sb2), one of three SNARE proteins involved in neuronal synaptic vesicle fusion. The three-dimensional crystal structure of the apo botulinum neurotoxin serotype B catalytic domain (BoNT/B-LC) has been determined to 2.2 A resolution, and the complex of cleaved Sb2 with the catalytic domain (Sb2-BoNT/B-LC) has been determined to 2.0 A resolution. A comparison of the holotoxin catalytic domain and the isolated BoNT/B-LC structure shows a rearrangement of three active site loops. This rearrangement exposes the BoNT/B active site. The Sb2-BoNT/B-LC structure illustrates two distinct binding regions, which explains the specificity of each botulinum neurotoxin for its synaptic vesicle protein. This observation provides an explanation for the proposed cooperativity between binding of full-length substrate and catalysis and suggest a mechanism of synaptobrevin proteolysis employed by the clostridial neurotoxins.
Department of Chemistry and Molecular Biology, The Scripps Research Institute, La Jolla, California 92037, USA.
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Hanson
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Stevens
D000595:Amino Acid Sequence; D001059:Apoproteins / Q000737:chemistry / Q000378:metabolism; D001665:Binding Sites; D001905:Botulinum Toxins / Q000737:chemistry* / Q000378:metabolism*; D019274:Botulinum Toxins, Type A; D002384:Catalysis; D020134:Catalytic Domain; D003014:Clostridium botulinum / Q000737:chemistry*; D018360:Crystallography, X-Ray; D008565:Membrane Proteins / Q000737:chemistry* / Q000378:metabolism*; D008956:Models, Chemical; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D050683:R-SNARE Proteins; D050600:SNARE Proteins; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D033921:Vesicular Transport Proteins
D001059:Apoproteins; D008565:Membrane Proteins; D010446:Peptide Fragments; D050683:R-SNARE Proteins; D050600:SNARE Proteins; D033921:Vesicular Transport Proteins; C096323:rimabotulinumtoxinB; D001905:Botulinum Toxins; D019274:Botulinum Toxins, Type A