Characterization of putative cholesterol recognition/interaction amino acid consensus-like motif of Campylobacter jejuni cytolethal distending toxin C.
Characterization of putative cholesterol recognition/interaction amino acid consensus-like motif of Campylobacter jejuni cytolethal distending toxin C.
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DOI：
10.1371/journal.pone.0066202
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Su HL
中科院分区：
文献类型：
--
作者：
Lai CH;Lai CK;Lin YJ;Hung CL;Chu CH;Feng CL;Chang CS;Su HL
空肠弯曲杆菌产生的细胞致死膨胀毒素（CDT）是由CdtA、CdtB和CdtC组成的异三聚体复合物。在这些毒素亚基中，CdtA和CdtC是介导毒素与细胞质膜结合并将CdtB传递到细胞核的必需蛋白。CdtA/CdtC与细胞表面的结合是由胆固醇介导的，胆固醇是脂筏的主要成分。虽然在一些细菌性病原体中已经报道了CDT的胆固醇识别/相互作用氨基酸共识（CRAC）结构域，但空肠梭菌中CDT与胆固醇结合的蛋白质区域仍不清楚。在这里，我们选择了空肠c的CdtC中存在的一个潜在的crac样区域进行分析。分子模型表明，预测的功能域具有疏水沟槽的形状，有助于胆固醇定位到该结构域。crac样区酪氨酸残基的突变减少了CdtC与胆固醇的直接结合，而不是毒素分子间的相互作用，从而导致CDT中毒受损。这些结果提供了空肠C. CdtC和膜脂筏之间通过crac样区域的分子联系，这有助于毒素识别和与胆固醇的相互作用。
Cytolethal distending toxin (CDT) produced by Campylobacter jejuni comprises a heterotrimeric complex formed by CdtA, CdtB, and CdtC. Among these toxin subunits, CdtA and CdtC function as essential proteins that mediate toxin binding to cytoplasmic membranes followed by delivery of CdtB into the nucleus. The binding of CdtA/CdtC to the cell surface is mediated by cholesterol, a major component in lipid rafts. Although the putative cholesterol recognition/interaction amino acid consensus (CRAC) domain of CDT has been reported from several bacterial pathogens, the protein regions contributing to CDT binding to cholesterol in C. jejuni remain unclear. Here, we selected a potential CRAC-like region present in the CdtC from C. jejuni for analysis. Molecular modeling showed that the predicted functional domain had the shape of a hydrophobic groove, facilitating cholesterol localization to this domain. Mutation of a tyrosine residue in the CRAC-like region decreased direct binding of CdtC to cholesterol rather than toxin intermolecular interactions and led to impaired CDT intoxication. These results provide a molecular link between C. jejuni CdtC and membrane-lipid rafts through the CRAC-like region, which contributes to toxin recognition and interaction with cholesterol.
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影响因子：
7.8
作者：
Abrami, L;Fivaz, M;Glauser, PE;Parton, RG;van der Goot, FG
通讯作者：
van der Goot, FG
影响因子：
4.8
作者：
Li, H;Papadopoulos, V
通讯作者：
Papadopoulos, V
影响因子：
3.1
作者：
Lin, Chia-Der;Lai, Cheng-Kuo;Lai, Chih-Ho
通讯作者：
Lai, Chih-Ho
影响因子：
64.8
作者：
Nesic, D;Hsu, Y;Stebbins, CE
通讯作者：
Stebbins, CE
DOI：
10.1083/jcb.200211018
发表时间：
2003-02-03
期刊：
The Journal of cell biology
影响因子：
--
作者：
Abrami L;Liu S;Cosson P;Leppla SH;van der Goot FG
通讯作者：
van der Goot FG