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.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 肺表面活性剂是肺部和蛋白质的混合物，肺部分泌涂层液体的薄层，该液体将肺泡空气空间排成一层。它的功能是降低表面张力，从而防止呼气结束时肺泡塌陷。两种疏水表面活性剂蛋白SPB和SP-C，构成完全混合物的1.5％（w/w），对于正常功能至关重要。蛋白质可促进表面活性剂囊泡吸附到空气/水界面上，从而使表面活性剂膜在婴儿第一次呼吸时形成初始表面的几秒钟内形成。尽管它们的重要性，但蛋白质促进吸附的机制尚不确定。提出的研究检验假设从一个模型中假设，在该模型中，蛋白质稳定了速率确定的负弯曲结构，该结构弥合了表面活性剂囊泡和空气/水接口之间的双层之间的间隙。我们的实验将确定是否：（1）分散成分，最初形成单层囊泡（ULV），可以通过小角度X射线散射（SAXS）检测到，必须转换为多层囊泡（MLV），以小角度X射线X射线衍射（SAXD）为准，从而衡量。 （2）SPS改变了脂质小叶的自发曲率，该脂质小叶是从六边形II（HII）结构的SAXD产生的D间距获得的； （3）SPS改变了弯曲模量，该模量是从带有和没有蛋白质的MLV产生的衍射峰的形状获得的。