Location of the Hydrophobic Surfactant Proteins, SP-B and SP-C, in Fluid-Phase Bilayers.
Location of the Hydrophobic Surfactant Proteins, SP-B and SP-C, in Fluid-Phase Bilayers.
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DOI：
10.1021/acs.jpcb.0c03665
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发表时间：
2020-08-06
期刊：
影响因子：
--
通讯作者：
Tristram-Nagle SA
中科院分区：
文献类型：
--
作者：
Loney RW;Panzuela S;Chen J;Yang Z;Fritz JR;Dell Z;Corradi V;Kumar K;Tieleman DP;Hall SB;Tristram-Nagle SA
疏水性表面活性剂蛋白 SP-B 和 SP-C 促进表面活性剂脂质快速吸附到肺泡气囊内的液体表面。为了深入了解其功能机制，我们使用 X 射线漫散射 (XDS) 和分子动力学 (MD) 模拟来确定 SP-B 和 SP-C 在磷脂双层内的位置。初始样品含有从小牛表面活性剂中提取的表面活性剂脂质，并且蛋白质剂量不断增加。 XDS 定位了磷脂头基附近和烃核心中的蛋白质密度，推测分别为 SP-B 和 SP-C。用蛋白质测量二油酰磷脂酰胆碱 (DOPC) 产生了相似的结果。使用 DOPC 对蛋白质进行 MD 模拟提供了分子细节，并可以直接比较实验结果和模拟结果。模拟使用基于皂苷样家族其他成员的 SP-B 构象，形成开放或封闭的 V 形结构。对于 SP-C，氨基酸序列表明有部分 α 螺旋。模拟最适合封闭 SP-B 的 XDS 测量（发生在膜表面）和沿着疏水内部定向的 SP-C。我们的结果提供了有关疏水性表面活性蛋白的位置和方向的最明确的证据。
The hydrophobic surfactant proteins, SP-B and SP-C, promote rapid adsorption by the surfactant lipids to the surface of the liquid that lines the alveolar air sacs of the lungs. To gain insights into the mechanisms of their function, we used X-ray diffuse scattering (XDS) and molecular dynamics (MD) simulations to determine the location of SP-B and SP-C within phospholipid bilayers. Initial samples contained the surfactant lipids from extracted calf surfactant with increasing doses of the proteins. XDS located protein density near the phospholipid headgroup and in the hydrocarbon core, presumed to be SP-B and SP-C, respectively. Measurements on dioleoylphosphatidylcholine (DOPC) with the proteins produced similar results. MD simulations of the proteins with DOPC provided molecular detail and allowed direct comparison of the experimental and simulated results. Simulations used conformations of SP-B based on other members of the saposin-like family, which form either open or closed V-shaped structures. For SP-C, the amino acid sequence suggests a partial α-helix. Simulations fit best with measurements of XDS for closed SP-B, which occurred at the membrane surface, and SP-C oriented along the hydrophobic interior. Our results provide the most definitive evidence yet concerning the location and orientation of the hydrophobic surfactant proteins.
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影响因子：
3.3
作者：
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