Cocrystal structure of synaptobrevin-II bound to botulinum neurotoxin type B at 2.0 Å resolution (Retracted article. See vol 16, pg 795, 2009)
Cocrystal structure of synaptobrevin-II bound to botulinum neurotoxin type B at 2.0 Å resolution (Retracted article. See vol 16, pg 795, 2009)
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DOI：
10.1038/77997
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发表时间：
2000-08-01
期刊：
影响因子：
--
通讯作者：
Stevens, RC
中科院分区：
文献类型：
--
作者：
Hanson, MA;Stevens, RC
肉毒杆菌神经毒素血清型B是一种锌蛋白酶，其通过切割突触小泡蛋白-II（Sb 2）来破坏神经递质释放，突触小泡蛋白-II是参与神经元突触囊泡融合的三种SNARE蛋白之一。载脂蛋白肉毒杆菌神经毒素血清型B催化结构域（BoNT/B-LC）的三维晶体结构已被确定为2.2埃分辨率，切割的Sb 2与催化结构域的复合物（Sb 2-BoNT/B-LC）已被确定为2.0埃分辨率。全毒素催化结构域和分离的BoNT/B-LC结构的比较显示了三个活性位点环的重排。这种重排暴露了BoNT/B活性位点。Sb 2-BoNT/B-LC结构说明了两个不同的结合区域，这解释了每种肉毒杆菌神经毒素对其突触囊泡蛋白的特异性。这一观察结果提供了一个解释的全长底物和催化的结合之间的建议的协同性，并建议采用梭菌神经毒素的小突触蛋白水解的机制。
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 Angstrom resolution, and the complex of cleaved Sb2 with the catalytic domain (Sb2-BoNT/B-LC) has been determined to 2.0 Angstrom 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.