2012年12月4日 訊 /生物谷BIOON/ --一個(gè)50多年來(lái)的未解之謎在今天終于有了答案,，近日,，來(lái)自于默奧大學(xué)的研究者詳細(xì)揭示了鈣促進(jìn)耶爾森氏菌引發(fā)疾病的分子機(jī)制,，相關(guān)研究成果刊登國(guó)際雜志PLoS ONE上,。
20世紀(jì)40年代,，黑死病殺死了帶走了歐洲三分之一人口的生命,，盡管鼠疫(耶爾森氏)桿菌被認(rèn)為在歐洲已經(jīng)絕跡了,，但是世界衛(wèi)生組織在非洲,、亞洲和美國(guó)報(bào)道依然有該病菌的疾病流行，耶爾森氏菌可以引發(fā)嚴(yán)重的胃腸疾病和痢疾的發(fā)生,。
20世紀(jì)50年代,，研究者提出了一個(gè)問(wèn)題，就是鈣如何幫助耶爾森氏菌引發(fā)疾病,，如今在這篇研究報(bào)告中,，研究者解釋了這個(gè)問(wèn)題的機(jī)制。
此前研究中,，研究者發(fā)現(xiàn),，一種特異性的蛋白質(zhì)YscU可以結(jié)合鈣，研究者認(rèn)為這是鈣發(fā)揮作用的一個(gè)重要部分,，如今研究者揭示了蛋白質(zhì)YscU的破壞是細(xì)菌引發(fā)感染的一個(gè)重要步驟,。
研究者M(jìn)agnus Wolf-Watz表示，運(yùn)用NMR（核磁共振波譜法）技術(shù),，我們可以揭示蛋白質(zhì)YscU與鈣結(jié)合的具體部位,，NMR可以幫助研究者確定分子的組分以及詳細(xì)結(jié)構(gòu)，運(yùn)用這項(xiàng)技術(shù),，研究者就可以輕松揭示鈣質(zhì)是如何幫助耶爾森氏菌引發(fā)機(jī)體感染的,。（生物谷Bioon.com）
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.
