PLoS ONE：揭示钙促进鼠疫（耶尔森氏菌）引发机体感染的分子机制

一个50多年来的未解之谜在今天终于有了答案，近日，来自于默奥大学的研究者详细揭示了钙促进耶尔森氏菌引发疾病的分子机制，相关研究成果刊登国际杂志PLoS ONE上。

20世纪40年代，黑死病杀死了带走了欧洲三分之一人口的生命，尽管鼠疫(耶尔森氏)杆菌被认为在欧洲已经绝迹了，但是世界卫生组织在非洲、亚洲和美国报道依然有该病菌的疾病流行，耶尔森氏菌可以引发严重的胃肠疾病和痢疾的发生。

20世纪50年代，研究者提出了一个问题，就是钙如何帮助耶尔森氏菌引发疾病，如今在这篇研究报告中，研究者解释了这个问题的机制。

此前研究中，研究者发现，一种特异性的蛋白质YscU可以结合钙，研究者认为这是钙发挥作用的一个重要部分，如今研究者揭示了蛋白质YscU的破坏是细菌引发感染的一个重要步骤。

研究者Magnus Wolf-Watz表示，运用NMR（核磁共振波谱法）技术，我们可以揭示蛋白质YscU与钙结合的具体部位，NMR可以帮助研究者确定分子的组分以及详细结构，运用这项技术，研究者就可以轻松揭示钙质是如何帮助耶尔森氏菌引发机体感染的。

doi:10.1371/journal.pone.0049349
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Autoproteolysis and Intramolecular Dissociation of Yersinia YscU Precedes Secretion of Its C-Terminal Polypeptide YscUCC

Stefan Frost1, Oanh Ho2, Frédéric H. Login1, Christoph F. Weise2, Hans Wolf-Watz1*, Magnus Wolf-Watz2*

Type III secretion system mediated secretion and translocation of Yop-effector proteins across the eukaryotic target cell membrane by pathogenic Yersinia is highly organized and is dependent on a switching event from secretion of early structural substrates to late effector substrates (Yops). Substrate switching can be mimicked in vitro by modulating the calcium levels in the growth medium. YscU that is essential for regulation of this switch undergoes autoproteolysis at a conserved N↑PTH motif, resulting in a 10 kDa C-terminal polypeptide fragment denoted YscUCC. Here we show that depletion of calcium induces intramolecular dissociation of YscUCC from YscU followed by secretion of the YscUCC polypeptide. Thus, YscUCC behaved in vivo as a Yop protein with respect to secretion properties. Further, destabilized yscU mutants displayed increased rates of dissociation of YscUCC in vitro resulting in enhanced Yop secretion in vivo at 30°C relative to the wild-type strain.These findings provide strong support to the relevance of YscUCC dissociation for Yop secretion. We propose that YscUCC orchestrates a block in the secretion channel that is eliminated by calcium depletion. Further, the striking homology between different members of the YscU/FlhB family suggests that this protein family possess regulatory functions also in other bacteria using comparable mechanisms.