STRUCTURAL EFFECTS OF HYDROPHOBIC SURFACTANT PROTEINS

疏水表面活性剂蛋白质的结构效应

• 批准号: 7954365
• 负责人: STEPHEN B HALL
• 金额: $ 0.02万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-03-01 至 2010-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7954365
• 关键词: Adsorption; Air; Alveolar; Computer Retrieval of Information on Scientific Projects Database; Exhalation; Film; Funding; Grant; Institution; Lipids; Liquid substance; Lung; Measures; Modeling; Proteins; Pulmonary Surfactant-Associated Protein A; Pulmonary Surfactants; Research; Research Personnel; Resources; Roentgen Rays; Shapes; Source; Structure; Surface; Surface Tension; Testing; United States National Institutes of Health; Vesicle; Water; X ray diffraction analysis; X-Ray Diffraction; prevent; research study; structural biology; surfactant; synchrotron radiation

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Pulmonary surfactant is the mixture of lipids and proteins that the lungs secrete to coat the thin layer of liquid that lines the alveolar air spaces. Its function is to lower surface tension, thereby preventing alveolar collapse at the end of exhalation. Two hydrophobic surfactant proteins, SPB and SP-C, which constitute less than 1.5% (w/w) of the complete mixture, are essential for normal function. The proteins promote adsorption of surfactant vesicles to the air/water interface, allowing surfactant films to form within seconds of creating the initial surface when a baby takes its first breath. Despite their importance, the mechanisms by which the proteins facilitate adsorption are uncertain. The proposed studies test hypotheses that follow from a model in which the proteins stabilize a rate-determining, negatively curved structure that bridges the gap between the bilayer of a surfactant vesicle and the air/water interface. Our experiments will determine if: (1) dispersed constituents, which initially form unilamellar vesicles (ULV) that can be detected by small angle X-ray scattering (SAXS), must transform to multilamellar vesicles (MLV), measured by small angle X-ray diffraction (SAXD), to adsorb rapidly; (2) the SPs alter the spontaneous curvature of lipid leaflets, obtained from the d-spacing produced by SAXD from hexagonal-II (HII) structures; (3) the SPs alter the bending modulus, obtained from the shape of the diffraction peaks generated by MLV with and without the proteins.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 肺表面活性物质是肺部分泌的脂质和蛋白质的混合物，用于覆盖肺泡空气空间内的薄薄一层液体。其功能是降低表面张力，从而防止呼气末肺泡塌陷。两种疏水性表面活性剂蛋白 SPB 和 SP-C 占完整混合物的比例不到 1.5% (w/w)，对于正常功能至关重要。这些蛋白质促进表面活性剂囊泡吸附到空气/水界面，使得表面活性剂薄膜在婴儿第一次呼吸时形成初始表面的几秒钟内形成。尽管它们很重要，但蛋白质促进吸附的机制尚不确定。拟议的研究测试了根据模型得出的假设，在该模型中，蛋白质稳定了决定速率的负弯曲结构，该结构桥接了表面活性剂囊泡双层与空气/水界面之间的间隙。我们的实验将确定是否：(1) 最初形成可通过小角 X 射线散射 (SAXS) 检测到的单层囊泡 (ULV) 的分散成分必须转变为多层囊泡 (MLV)，通过小角 X 射线测量射线衍射（SAXD），快速吸附； (2) SP 改变了脂质小叶的自发曲率，该曲率是通过 SAXD 从六角形 II (HII) 结构产生的 d 间距获得的； (3) SP 改变了弯曲模量，该模量是从含有和不含有蛋白质的 MLV 产生的衍射峰的形状获得的。