SP-A permeabilizes lipopolysaccharide membranes by forming protein aggregates that extract lipids from the membrane
SP-A permeabilizes lipopolysaccharide membranes by forming protein aggregates that extract lipids from the membrane
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DOI：
10.1529/biophysj.108.137323
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发表时间：
2008-10-01
影响因子：
3.4
通讯作者：
Casals, Cristina
中科院分区：
文献类型：
--
作者：
Canadas, Olga;Garcia-Verdugo, Ignacio;Casals, Cristina
已知表面活性剂蛋白A（SP-A）引起细菌透化。本工作的目的是深入了解SP-A诱导粗脂多糖（Re-LPS）膜透化的机制。在钙的存在下，荧光标记的TR-SP-A的大的相互连接的聚集体上的Re-LPS膜的表面上观察到通过落射荧光显微镜。使用Re-LPS单层松弛实验在恒定的表面压力下，我们证明，SP-A诱导Re-LPS分子损失，通过促进形成三维脂质-蛋白质聚集体在Re-LPS膜。这导致Re-LPS酰基链之间的货车范德华相互作用降低，如通过差示扫描量热法测定的，这使得膜渗漏。我们还表明，凝胶和液体脂质相的Re-LPS膜内的共存赋予敏感性SP-A介导的透化。总而言之，我们的结果似乎表明SP-A对Re-LPS膜的钙依赖性透化与由于形成含有LPS的钙介导的蛋白聚集体而从膜中提取LPS分子有关。
Surfactant protein A (SP-A) is known to cause bacterial permeabilization. The aim of this work was to gain insight into the mechanism by which SP-A induces permeabilization of rough lipopolysaccharide (Re-LPS) membranes. In the presence of calcium, large interconnected aggregates of fluorescently labeled TR-SP-A were observed on the surface of Re-LPS films by epifluorescence microscopy. Using Re-LPS monolayer relaxation experiments at constant surface pressure, we demonstrated that SP-A induced Re-LPS molecular loss by promoting the formation of three-dimensional lipid-protein aggregates in Re-LPS membranes. This resulted in decreased van der Waals interactions between Re-LPS acyl chains, as determined by differential scanning calorimetry, which rendered the membrane leaky. We also showed that the coexistence of gel and fluid lipid phases within the Re-LPS membrane conferred susceptibility to SP-A-mediated permeabilization. Taken together, our results seem to indicate that the calcium-dependent permeabilization of Re-LPS membranes by SP-A is related to the extraction of LPS molecules from the membrane due to the formation of calcium-mediated protein aggregates that contain LPS.