Interplay between predicted inner-rod and gatekeeper in controlling substrate specificity of the type III secretion system
Interplay between predicted inner-rod and gatekeeper in controlling substrate specificity of the type III secretion system
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DOI：
10.1111/mmi.12158
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发表时间：
2013-03-01
影响因子：
3.6
通讯作者：
Botteaux, Anne
中科院分区：
文献类型：
--
作者：
Cherradi, Youness;Schiavolin, Lionel;Botteaux, Anne
III型分泌器（T3SA）是许多革兰氏阴性病原体的毒力的核心的多蛋白复合物。目前，对控制针亚基、移位器和效应器到T3SA的分级寻址的机制仍然知之甚少。在志贺氏菌中，已知MxiC在从针接收激活信号之前将效应物隔离在细胞质内。然而，参与连接针和MxiC的分子是未知的。在这里，我们展示了MxiC和预测的内杆组件MxiI之间的分子相互作用，这表明该复合物堵塞了T3SA入口门。我们的研究结果表明，MxiIMxiC复合物解离促进了分泌从转运子到效应子的转换。我们鉴定了MxiCF206S变体，其不能与MxiI相互作用，其表现出组成型分泌表型，尽管其仍然对诱导有响应。此外，我们鉴定了仅分泌易位子的mxiIQ67A突变体，这是一种被MxiCF206S变体的共表达抑制的表型。我们证明了在耶尔森氏菌和沙门氏菌中MxiI和MxiC同源物之间的相互作用。最后，我们确定了MxiC和分子伴侣IpgC之间的相互作用，这有助于理解如何调节转运子分泌。总之，这项研究表明，存在一个广泛保守的T3S机制，调节效应分泌。
The type III secretion apparatus (T3SA) is a multi-protein complex central to the virulence of many Gram-negative pathogens. Currently, the mechanisms controlling the hierarchical addressing of needle subunits, translocators and effectors to the T3SA are still poorly understood. In Shigella, MxiC is known to sequester effectors within the cytoplasm prior to receiving the activation signal from the needle. However, molecules involved in linking the needle and MxiC are unknown. Here, we demonstrate a molecular interaction between MxiC and the predicted inner-rod component MxiI suggesting that this complex plugs the T3SA entry gate. Our results suggest that MxiIMxiC complex dissociation facilitates the switch in secretion from translocators to effectors. We identified MxiCF206S variant, unable to interact with MxiI, which exhibits a constitutive secretion phenotype although it remains responsive to induction. Moreover, we identified the mxiIQ67A mutant that only secretes translocators, a phenotype that was suppressed by coexpression of the MxiCF206S variant. We demonstrated the interaction between MxiI and MxiC homologues in Yersinia and Salmonella. Lastly, we identified an interaction between MxiC and chaperone IpgC which contributes to understanding how translocators secretion is regulated. In summary, this study suggests the existence of a widely conserved T3S mechanism that regulates effectors secretion.