Penetration Depth of Surfactant Peptide KL4 into Membranes Is Determined by Fatty Acid Saturation
Penetration Depth of Surfactant Peptide KL4 into Membranes Is Determined by Fatty Acid Saturation
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DOI：
10.1016/j.bpj.2008.12.3966
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发表时间：
2009-05-20
影响因子：
3.4
通讯作者：
Long, Joanna R.
中科院分区：
文献类型：
--
作者：
Antharam, Vijay C.;Elliott, Douglas W.;Long, Joanna R.
KL4是肺表面活性剂蛋白B的21个残基功能肽模拟物，是降低肺泡表面张力的必需蛋白。通过圆二色性、差示扫描量热法和固态核磁共振光谱研究了其改变脂质性质和恢复肺顺应性的能力。KL4结合流体层状相PC/PG脂质膜，形成两亲螺旋，改变脂质组织和酰基链动力学。KL4的结合和螺旋度取决于脂肪酸链中的单不饱和水平。在生理温度下，KL4在液相POPC/POPG mlv中更具有外围性和动态性，但被深入插入液相DPPC/POPG囊泡中，导致肽的固定化。随着KL4水平的升高，DPPC/POPG脂囊的酰基链序显著增加，而在添加KL4时，POPC/POPG脂囊的酰基链序参数略有下降。此外，KL4对流体相PG头群的取向有明显的影响，在两种脂质环境中也有类似的变化。在接近DPPC/POPG脂质混合物的相变温度（略低于肺表面活性剂的生理温度）时，KL4导致相分离，DPPC保持在凝胶相，而POPG在凝胶相和流体相之间分裂。KL4分化成含有不同单不饱和水平的脂质薄片的能力以及随后曲率应变的变化表明，在动态肺环境中，肽介导的脂质组织和运输的机制。
KL4 is a 21-residue functional peptide mimic of lung surfactant protein B, an essential protein for lowering surface tension in the alveoli. Its ability to modify lipid properties and restore lung compliance was investigated with circular dichroism, differential scanning calorimetry, and solid-state NMR spectroscopy. KL4 binds fluid lamellar phase PC/PG lipid membranes and forms an amphipathic helix that alters lipid organization and acyl chain dynamics. The binding and helicity of KL4 is dependent on the level of monounsaturation in the fatty acid chains. At physiologic temperatures, KL4 is more peripheral and dynamic in fluid phase POPC/POPG MLVs but is deeply inserted into fluid phase DPPC/POPG vesicles, resulting in immobilization of the peptide. Substantial increases in the acyl chain order are observed in DPPC/POPG lipid vesicles with increasing levels of KL4, and POPC/POPG lipid vesicles show small decreases in the acyl chain order parameters on addition of KL4. Additionally, a clear effect of KL4 on the orientation of the fluid phase PG headgroups is observed, with similar changes in both lipid environments. Near the phase transition temperature of the DPPC/POPG lipid mixtures, which is just below the physiologic temperature of lung surfactant, KL4 causes phase separation with the DPPC remaining in a gel phase and the POPG partitioned between gel and fluid phases. The ability of KL4 to differentially partition into lipid lamellae containing varying levels of monounsaturation and subsequent changes in curvature strain suggest a mechanism for peptide-mediated lipid organization and trafficking within the dynamic lung environment.