Conservation of the biochemical properties of IncA from Chlamydia trachomatis and Chlamydia caviae -: Oligomerization of IncA mediates interaction between facing membranes
Conservation of the biochemical properties of IncA from Chlamydia trachomatis and Chlamydia caviae -: Oligomerization of IncA mediates interaction between facing membranes
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DOI：
10.1074/jbc.m407227200
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发表时间：
2004-11-05
影响因子：
4.8
通讯作者：
Subtil, A
中科院分区：
文献类型：
--
作者：
Delevoye, C;Nilges, M;Subtil, A
衣原体科的发育周期发生在一个称为包容的膜室中。印加人是通过细菌合成并分泌到包含膜的蛋白质家族的成员。来自不同种类的衣原体科的印加蛋白几乎没有序列相似性。我们报告说，沙眼衣原体和衣原体Caviae的生化特性是保守的。两种蛋白质都可以自我关联以形成多聚体。当宿主细胞人为地表达时，它们位于内质网。引人注目的是，内质网中INCA的异源表达完全抑制了伴随的纳入发展。使用C. caviae的INCA截短形式，我们表明蛋白质在内质网表面的C末端细胞质结构域的表达足以破坏细菌发育周期。另一方面，人工印加表达不会抑制未表达印加的沙眼霉菌菌株的发展，这表明用野生型菌株观察到的破坏性效应需要在包含和内质上的INCA分子之间直接相互作用网状。最后，我们根据SNARE复合物的结构（一种涉及真核细胞膜融合的保守结构）在平行的四个螺旋束中对Inca四聚体进行了建模。在该模型中，沙眼梭状疱疹和C. caviae Inca四聚体均高度稳定。总之，我们表明，在衣原体物种之间保守了印加蛋白聚集成多聚体结构的特性，并且我们建议这些蛋白质可能已经与圈套机械共同发展，以在膜融合中发挥作用。
The developmental cycle of Chlamydiaceae occurs in a membrane compartment called an inclusion. IncA is a member of a family of proteins synthesized and secreted onto the inclusion membrane by bacteria. IncA proteins from different species of Chlamydiaceae show little sequence similarity. We report that the biochemical properties of Chlamydia trachomatis and Chlamydia caviae are conserved. Both proteins self-associate to form multimers. When artificially expressed by the host cell, they localize to the endoplasmic reticulum. Strikingly, heterologous expression of IncA in the endoplasmic reticulum completely inhibits concomitant inclusion development. Using truncated forms of IncA from C. caviae, we show that expression of the C-terminal cytoplasmic domain of the protein at the surface of the endoplasmic reticulum is sufficient to disrupt the bacterial developmental cycle. On the other hand, development of a C. trachomatis strain that does not express IncA is not inhibited by artificial IncA expression, showing that the disruptive effect observed with the wild-type strain requires direct interactions between IncA molecules at the inclusion and on the endoplasmic reticulum. Finally, we modeled IncA tetramers in parallel four helix bundles based on the structure of the SNARE complex, a conserved structure involved in membrane fusion in eukaryotic cells. Both C. trachomatis and C. caviae IncA tetramers were highly stable in this model. In conclusion, we show that the property of IncA proteins to assemble into multimeric structures is conserved between chlamydial species, and we propose that these proteins may have co-evolved with the SNARE machinery for a role in membrane fusion.