PDF(Pubmed)
Abstract：
Typhoid toxin is a virulence factor for the bacterial pathogen Salmonella Typhi, which causes typhoid fever in humans. After its synthesis by intracellular bacteria, typhoid toxin is secreted into the lumen of the Salmonella-containing vacuole by a secretion mechanism strictly dependent on TtsA, a specific muramidase that facilitates toxin transport through the peptidoglycan layer. Here we show that substrate recognition by TtsA depends on a discrete domain within its carboxy terminus, which targets the enzyme to the bacterial poles to recognize YcbB-edited peptidoglycan. Comparison of the atomic structures of TtsA bound to its substrate and that of a close homolog with different specificity identified specific determinants involved in substrate recognition. Combined with structure-guided mutagenesis and in vitro and in vivo crosslinking experiments, this study provides an unprecedented view of the mechanisms by which a muramidase recognizes its peptidoglycan substrate to facilitate protein secretion.
摘要：
伤寒毒素是细菌病原体伤寒沙门氏菌的毒力因子，导致人类伤寒。由胞内细菌合成后，伤寒毒素通过严格依赖于TtsA的分泌机制分泌到含沙门氏菌的液泡腔中，一种促进毒素通过肽聚糖层转运的特定的鼠酰胺酶。在这里，我们显示TtsA的底物识别取决于其羧基末端内的离散结构域，它将酶靶向细菌两极以识别YcbB编辑的肽聚糖。与底物结合的TtsA原子结构和具有不同特异性的紧密同源物的原子结构的比较确定了参与底物识别的特定决定子。结合结构引导诱变和体内外交联实验，这项研究提供了一个前所未有的观点，其中muramidase识别其肽聚糖底物，以促进蛋白质分泌的机制。
