Dimeric Structure of the Bacterial Extracellular Foldase PrsA
Dimeric Structure of the Bacterial Extracellular Foldase PrsA
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DOI：
10.1074/jbc.m114.622910
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发表时间：
2015-02-06
影响因子：
4.8
通讯作者：
Maier, Timm
中科院分区：
文献类型：
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作者：
Jakob, Roman P.;Koch, Johanna R.;Maier, Timm
在革兰氏阳性菌中，蛋白质分泌到膜-细胞壁空间对于细胞壁的生物合成和致病性是必不可少的。许多分泌蛋白质的折叠和成熟依赖于单一的细胞外折叠酶，即PRSA蛋白。PRSA是一种30 kDa的蛋白质，脂类固定在细胞膜的外层小叶上。枯草芽孢杆菌PRSA的晶体结构显示了一个中心催化的小豆素型丙酰异构酶结构域，它被插入到由N-末端和C-末端形成的更大的复合NC结构域中。这个结构域结构类似于触发因子和SurA，尽管缺乏序列保守，但两者都是核糖体结合的细菌伴侣，而SurA是革兰氏阴性细菌的周质伴侣。观察到两个主要的结构差异在于PRSA的N-末端臂相对于触发因子和SurA显著缩短，以及PRSA被发现通过其NC结构域以独特的方式二聚。二聚作用导致一个大的碗状缝隙，这可能在体内参与保护底物蛋白免受聚集。NMR实验表明，小球蛋白和NC结构域与分泌的前肽之间存在直接的、动态的相互作用，这与底物靶向PRSA有关。
Secretion of proteins into the membrane-cell wall space is essential for cell wall biosynthesis and pathogenicity in Gram-positive bacteria. Folding and maturation of many secreted proteins depend on a single extracellular foldase, the PrsA protein. PrsA is a 30-kDa protein, lipid anchored to the outer leaflet of the cell membrane. The crystal structure of Bacillus subtilis PrsA reveals a central catalytic parvulin-type prolyl isomerase domain, which is inserted into a larger composite NC domain formed by the N- and C-terminal regions. This domain architecture resembles, despite a lack of sequence conservation, both trigger factor, a ribosome-binding bacterial chaperone, and SurA, a periplasmic chaperone in Gram-negative bacteria. Two main structural differences are observed in that the N-terminal arm of PrsA is substantially shortened relative to the trigger factor and SurA and in that PrsA is found to dimerize in a unique fashion via its NC domain. Dimerization leads to a large, bowl-shaped crevice, which might be involved in vivo in protecting substrate proteins from aggregation. NMRexperiments reveal a direct, dynamic interaction of both the parvulin and the NC domain with secretion propeptides, which have been implicated in substrate targeting to PrsA.