2.3 Å crystal structure of tetanus neurotoxin light chain
2.3 Å crystal structure of tetanus neurotoxin light chain
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DOI：
10.1021/bi050262j
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发表时间：
2005-05-24
期刊：
影响因子：
2.9
通讯作者：
Brunger, AT
中科院分区：
文献类型：
--
作者：
Breidenbach, MA;Brunger, AT
TeNT是神经麻痹性疾病破伤风的病原体。靶向SNARE的TeNT（2+）内肽酶的关键组分。最近的结构研究密切相关的是它的轻链，一个Zn（2+），BoNT内肽酶表明，底物结合的外位点远离保守的活性位点是底物特异性的主要决定因素。在这里，我们报告的2.3埃的TeNTLC的X-射线晶体结构，结合分子置换和MAD定相。正如预期的那样，TeNT-LC的整体结构与其他已知的CNT轻链结构相似，包括插入结构上不同的氨基和羧基末端区域之间的保守嗜热菌蛋白酶样核心。TeNT-LC和其他CNT轻链之间的差异主要限于表面特征，如独特的静电势分布。表面残基保守性的分析揭示了一种模式，相对较高的可变性匹配的路径周围的BoNT/A的底物结合，可能有助于适应不同的SNARE目标的CNT组的变化。
TeNT is the causative agent of the neuroparalytic disease tetanus. A key component of TeNT (2+) endopeptidase that targets SNAREs. Recent structural studies of closely related is its light chain, a Zn (2+), BoNT endopeptidases indicate that substrate-binding exosites remote from a conserved active site are the primary determinants of substrate specificity. Here we report the 2.3 angstrom X-ray crystal structure of TeNTLC, determined by combined molecular replacement and MAD phasing. As expected, the overall structure of TeNT-LC is similar to the other known CNT light chain structures, including a conserved thermolysinlike core inserted between structurally distinct amino- and carboxy-terminal regions. Differences between TeNT-LC and the other CNT light chains are mainly limited to surface features such as unique electrostatic potential profiles. An analysis of surface residue conservation reveals a pattern of relatively high variability matching the path of substrate binding around BoNT/A, possibly serving to accommodate the variations in different SNARE targets of the CNT group.