Crystal structure of botulinum neurotoxin type G light chain: Serotype divergence in substrate recognition
Crystal structure of botulinum neurotoxin type G light chain: Serotype divergence in substrate recognition
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DOI：
10.1021/bi0505924
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发表时间：
2005-07-19
期刊：
影响因子：
2.9
通讯作者：
Stevens, RC
中科院分区：
文献类型：
--
作者：
Arndt, JW;Yu, W;Stevens, RC
肉毒杆菌神经毒素 (BoNT) 的七种血清型 (A-G) 通过对可溶性 N-乙基马来酰亚胺敏感因子附着蛋白受体 (SNARE) 复合物的三种蛋白质之一进行特异性蛋白水解来阻止神经递质释放。 BoNT 具有严格的底物特异性，这是金属蛋白酶所独有的，因为它们需要特别长的底物 (1)。为了了解 BoNT 独特特异性的分子原因，我们以 2.35 埃分辨率测定了 G 型肉毒杆菌神经毒素 (BoNT/G-LC) 催化轻链 (LC) 的晶体结构。 BoNT/G-LC 的结构揭示了 C 端 β-折叠，这对于 LC 寡聚化至关重要，并且与其他 LC 结构中所见的不同。其与嗜热菌蛋白酶的结构比较和可用的 LC 结构库揭示了重要的血清型差异，这些差异可能与 P1' 残基的底物识别有关。此外，结构和序列分析还发现了 BoNT/G-LC 的一个潜在外部位点，该位点可识别 VAMP 的 SNARE 识别基序。
The seven serotypes (A-G) of botulinum neurotoxins (BoNTs) block neurotransmitter release through their specific proteolysis of one of the three proteins of the soluble N-ethylmaleimide-sensitive-factor attachment protein receptor (SNARE) complex. BoNTs have stringent substrate specificities that are unique for metalloprotease in that they require exceptionally long substrates (1). To understand the molecular reasons for the unique specificities of the BoNTs, we determined the crystal structure of the catalytic light chain (LC) of Clostridium botulinum neurotoxin type G (BoNT/G-LC) at 2.35 angstrom resolution. The structure of BoNT/G-LC reveals a C-terminal beta-sheet that is critical for LC oligomerization and is unlike that seen in the other LC structures. Its structural comparison with thermolysin and the available pool of LC structures reveals important serotype differences that are likely to be involved in substrate recognition of the P1' residue. In addition, structural and sequence analyses have identified a potential exosite of BoNT/G-LC that recognizes a SNARE recognition motif of VAMP.