Lipid Polymorphism Induced by Surfactant Peptide SP-B1-25
Lipid Polymorphism Induced by Surfactant Peptide SP-B1-25
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DOI：
10.1016/j.bpj.2010.06.076
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发表时间：
2010-09-22
影响因子：
3.4
通讯作者：
Long, Joanna R.
中科院分区：
文献类型：
--
作者：
Farver, R. Suzanne;Mills, Frank D.;Long, Joanna R.
肺表面活性物质蛋白B （SP-B）是降低肺泡表面张力的必需蛋白。SP-B1-25是由SP-B的n端25个氨基酸残基组成的肽，已知保留了SP-B的大部分生物活性。圆二色性表明，当SP-B1-25与带负电荷的脂质囊泡相互作用时，它含有重要的螺旋结构，用于研究脂质组成和肽/脂质比率。通过DSC、动态光散射、透射电镜和固态核磁共振光谱研究SP-B1-25对脂质组织和多态性的影响。在1-3 mol%肽和生理温度下，SP-B1-25在带负电荷的PC/PG脂质双分子层界面上分裂。在含有1-5 mol%肽的脂质混合物中，SP-B1-25的结构保持不变，但H-2和P-31核磁共振光谱显示，在脂质T-m以下，存在各向同性的脂质相，与层状相交换。DPPC/POPG和POPC/POPG脂质混合物以及混合物中的PC和PG组分均观察到这种行为。对于1-3 mol% SP-B1-25，观察到脂质混合物T-m以上的单层相，但对于5 mol% SP-B1-25，在生理温度下观察到DPPC的显著各向同性成分，并且在两种混合物中其他脂质成分的H-2和P-31 NMR光谱中观察到交换展宽。DLS和TEM排除了胶束结构的形成，表明SP-B1-25促进了流体各向同性相的形成。SP-B1-25通过这种机制融合脂片的能力，特别是那些富含DPPC的脂片，表明SP-B高度保守的n端在脂片堆积成表面活性剂片层体或稳定气液界面多层结构中起着特殊作用。重要的是，在SP-B8-25和SP-B59-80的其他SP-B片段中没有发现这种行为，这表明富含脯氨酸的前7个氨基酸在该蛋白中起着关键作用。
Pulmonary surfactant protein B (SP-B) is an essential protein for lowering surface tension in the alveoli. SP-B1-25, a peptide comprised of the N-terminal 25 amino-acid residues of SP-B, is known to retain much of the biological activity of SP-B. Circular dichroism has shown that when SP-B1-25 interacts with negatively charged lipid vesicles, it contains significant helical structure for the lipid compositions and peptide/lipid ratios studied here. The effect of SP-B1-25 on lipid organization and polymorphisms was investigated via DSC, dynamic light scattering, transmission electron microscopy, and solid-state NMR spectroscopy. At 1-3 mol% peptide and physiologic temperature, SP-B1-25 partitions at the interface of negatively charged PC/PG lipid bilayers. In lipid mixtures containing 1-5 mol% peptide, the structure of SP-B1-25 remains constant, but H-2 and P-31 NMR spectra show the presence of an isotropic lipid phase in exchange with the lamellar phase below the T-m of the lipids. This behavior is observed for both DPPC/POPG and POPC/POPG lipid mixtures as well as for both the PC and PG components of the mixtures. For 1-3 mol% SP-B1-25, a return to a single lamellar phase above the lipid mixture T-m is observed, but for 5 mol% SP-B1-25 a significant isotropic component is observed at physiologic temperatures for DPPC and exchange broadening is observed in H-2 and P-31 NMR spectra of the other lipid components in the two mixtures. DLS and TEM rule out the formation of micellar structures and suggest that SP-B1-25 promotes the formation of a fluid isotropic phase. The ability of SP-B1-25 to fuse lipid lamellae via this mechanism, particularly those enriched in DPPC, suggests a specific role for the highly conserved N-terminus of SP-B in the packing of lipid lamellae into surfactant lamellar bodies or in stabilizing multilayer structures at the air-liquid interface. Importantly, this behavior has not been seen for the other SP-B fragments of SP-B8-25 and SP-B59-80, indicating a critical role for the proline rich first seven amino acids in this protein.