Secondary structure and lipid interactions of the N-terminal segment of pulmonary surfactant SP-C in Langmuir films: IR reflection-absorption spectroscopy and surface pressure studies
Secondary structure and lipid interactions of the N-terminal segment of pulmonary surfactant SP-C in Langmuir films: IR reflection-absorption spectroscopy and surface pressure studies
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DOI：
10.1021/bi020129g
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发表时间：
2002-07-02
期刊：
影响因子：
2.9
通讯作者：
Mendelsohn, R
中科院分区：
文献类型：
--
作者：
Bi, XH;Flach, CR;Mendelsohn, R
肺表面活性物质是哺乳动物肺内的一层薄薄的脂质/蛋白质膜，在体内起着减少呼吸功和防止肺泡塌陷的作用。两种疏水表面活性剂蛋白SP-B和SP-C的类似物已被掺入呼吸窘迫综合征的治疗剂中，呼吸窘迫综合征是由表面活性剂缺乏引起的病理状况。为了促进合理设计的治疗药物，在水单层膜的表面活性剂蛋白质或其类似物的脂质相互作用的分子水平的理解是必要的。目前的工作使用红外反射-吸收光谱（IRRAS）来确定肽构象和S-棕榈酰化对SP-C的合成13个残基N-末端肽[SP-C13（棕榈）（2）]与1，2-二棕榈酰磷脂酰胆碱（DPPC）或1，2-二棕榈酰磷脂酰甘油（DPPG）混合物中的脂质相互作用的影响。在肽的IRRAS光谱中，两个类似于1655和类似于1639 cm（-1）的酰胺I'特征分别归属于疏水和水环境中的α-螺旋肽键。在二元DPPC/SP-C13（棕榈）（2）膜中，水合/疏水螺旋的比例随着表面压力（pi）可逆地增加，表明肽从单层的疏水区域被挤出。DPPG/肽单层没有观察到这样的效果，表明更强的，可能是静电，相互作用。从IRRAS光谱和π-面积等温线推断，Depalinitoylation与磷脂的相互作用减弱。S-棕榈酰化可以调节SP-C的N-末端区域中的肽水合和构象，并且因此可以允许肽在肺压缩期间存在的高表面压力下保留在膜中。IRRAS的独特能力，以检测蛋白质或肽的结构/相互作用的表面压力依赖性的生理相关的表面活性剂模型清楚地表明。
Pulmonary surfactant, a thin lipid/protein film lining mammalian lungs, functions in vivo to reduce the work of breathing and to prevent alveolar collapse. Analogues of two hydrophobic surfactant proteins, SP-B and SP-C, have been incorporated into therapeutic agents for respiratory distress syndrome, a pathological condition resulting from deficiency in surfactant. To facilitate rational design of therapeutic agents, a molecular level understanding of lipid interaction with surfactant proteins or their analogues in aqueous monolayer films is necessary. The current work uses infrared reflection-absorption spectroscopy (IRRAS) to determine peptide conformation and the effects of S-palmitoylation on the lipid interactions of a synthetic 13 residue N-terminal peptide [SP-C13(palm)(2)] of SP-C, in mixtures with 1,2-dipalmitoylphosphatidylcholine (DPPC) or 1,2-dipalmitoylphosphatidylglycerol (DPPG). Two Amide I' features, at similar to1655 and similar to1639 cm(-1) in the peptide IRRAS spectra, are assigned to alpha-helical peptide bonds in hydrophobic and aqueous environments, respectively. In binary DPPC/SP-C13(palm)(2) films, the proportion of hydrated/hydrophobic helix increases reversibly with surface pressure (pi), suggestive of the peptide being squeezed out from hydrophobic regions of the monolayer. No such effect was observed for DPPG/peptide monolayers, indicative of stronger, probably electrostatic, interactions. Depalinitoylation produced a weakened interaction with either phospholipid as deduced from IRRAS spectra and from pi-area isotherms. S-Palmitoylation may modulate peptide hydration and conformation in the N-terminal region of SP-C and may thus permit the peptide to remain in the film at the high surface pressures present during lung compression. The unique capability of IRRAS to detect the surface pressure dependence of protein or peptide structure/interactions in a physiologically relevant model for surfactant is clearly demonstrated.