Nickerson Nicholas N, Joag Vineet, McGavin Martin J
Department of Laboratory Medicine and Pathobiology, University of Toronto Sunnybrook Health Sciences Centre, Toronto, ON M4N 3M5, Canada.
Mol Microbiol. 2008 Sep;69(6):1530-43. doi: 10.1111/j.1365-2958.2008.06384.x. Epub 2008 Jul 30.
The Staphylococcus aureus proteolytic cascade consists of a metalloprotease aureolysin (Aur), which activates a serine protease zymogen proSspA, which in turn activates the SspB cysteine protease. As with other M4 metalloproteases, including elastase of Pseudomonas aeruginosa, the propeptide of proAur contains an N-terminal fungalysin-thermolysin-propeptide (FTP) domain. Autocatalytic activation of proAur was initiated by processing at T85 downward arrowL(86) in the FTP domain. This differed from the mechanism described for proElastase, where the FTP domain has an RY motif in place of TL(86), and processing occurred at the junction of the propeptide and metalloprotease domains, which remained as an inactive complex during passage across the outer membrane. When TL(86) in the FTP domain was replaced with RY, an intact N-terminal propeptide was secreted, but the M4 metalloprotease domain was degraded. Consequently, this segment of the FTP domain promotes intramolecular processing of proAur while bestowing a chaperone function, but discourages processing within the FTP domain of proElastase, where activation must be co-ordinated with passage across a second membrane. We conclude that the FTP domain of proAur is adapted to facilitate a rapid autocatalytic activation mechanism, consistent with the role or proAur as initiator of the staphylococcal proteolytic cascade.
金黄色葡萄球菌蛋白水解级联反应由一种金属蛋白酶奥罗溶素（Aur）组成，它激活丝氨酸蛋白酶原proSspA，而proSspA又激活SspB半胱氨酸蛋白酶。与其他M4金属蛋白酶一样，包括铜绿假单胞菌的弹性蛋白酶，proAur的前肽包含一个N端真菌溶素-嗜热菌蛋白酶前肽（FTP）结构域。proAur的自催化激活是通过在FTP结构域的T85↓L(86)处进行加工启动的。这与pro弹性蛋白酶所描述的机制不同，在pro弹性蛋白酶中，FTP结构域有一个RY基序代替TL(86)，加工发生在前肽和金属蛋白酶结构域的交界处，在穿过外膜的过程中，该交界处仍作为一个无活性的复合物。当FTP结构域中的TL(86)被RY取代时，完整的N端前肽被分泌出来，但M4金属蛋白酶结构域被降解。因此，FTP结构域的这一部分促进了proAur的分子内加工，同时赋予了伴侣功能，但阻碍了pro弹性蛋白酶的FTP结构域内的加工，在pro弹性蛋白酶中，激活必须与穿过第二膜的过程相协调。我们得出结论，proAur的FTP结构域适合于促进快速的自催化激活机制，这与proAur作为葡萄球菌蛋白水解级联反应启动子的作用一致。
