Coutte L, Antoine R, Drobecq H, Locht C, Jacob-Dubuisson F
INSERM U447, IBL, Institut Pasteur de Lille, 1 rue Calmette, 59019 Lille Cedex, France.
EMBO J. 2001 Sep 17;20(18):5040-8. doi: 10.1093/emboj/20.18.5040.
Proteins of Gram-negative bacteria destined to the extracellular milieu must cross the two cellular membranes and then fold at the appropriate time and place. The synthesis of a precursor may be a strategy to maintain secretion competence while preventing aggregation or premature folding (especially for large proteins). The secretion of 230 kDa filamentous haemagglutinin (FHA) of Bordetella pertussis requires the synthesis and the maturation of a 367 kDa precursor that undergoes the proteolytic removal of its approximately 130 kDa C-terminal intramolecular chaperone domain. We have identified a specific protease, SphB1, responsible for the timely maturation of the precursor FhaB, which allows for extracellular release of FHA. SphB1 is a large exported protein with a subtilisin-like domain and a C-terminal domain typical of bacterial autotransporters. SphB1 is the first described subtilisin-like protein that serves as a specialized maturation protease in a secretion pathway of Gram-negative bacteria. This is reminiscent of pro-protein convertases of eukaryotic cells.
革兰氏阴性菌中注定要分泌到细胞外环境的蛋白质必须穿过两层细胞膜，然后在合适的时间和地点进行折叠。合成前体可能是一种在防止聚集或过早折叠（特别是对于大蛋白）的同时维持分泌能力的策略。百日咳博德特氏菌230 kDa丝状血凝素（FHA）的分泌需要合成和成熟一个367 kDa的前体，该前体经过蛋白水解去除其约130 kDa的C端分子内伴侣结构域。我们鉴定出一种特定的蛋白酶SphB1，它负责前体FhaB的适时成熟，从而使FHA能够释放到细胞外。SphB1是一种大型分泌蛋白，具有一个枯草杆菌蛋白酶样结构域和一个典型的细菌自转运蛋白C端结构域。SphB1是第一个被描述的在革兰氏阴性菌分泌途径中作为专门成熟蛋白酶的枯草杆菌蛋白酶样蛋白。这让人联想到真核细胞的前体蛋白转化酶。
