Membrane-dependent oligomeric structure and pore formation of β-hairpin antimicrobial peptide in lipid bilayers from solid-state NMR
Membrane-dependent oligomeric structure and pore formation of β-hairpin antimicrobial peptide in lipid bilayers from solid-state NMR
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DOI：
10.1073/pnas.0605079103
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发表时间：
2006-10-31
影响因子：
11.1
通讯作者：
Hong, Mei
中科院分区：
文献类型：
--
作者：
Mani, Rajeswari;Cady, Sarah D.;Hong, Mei
我们使用固态核磁共振光谱研究低聚体结构和插入的protegrin-1（PG-1），β-发夹抗菌肽，在脂质双层，模拟细菌内膜[棕榈酰油酰磷脂酰乙醇胺和棕榈酰油酰磷脂酰甘油（POPE/POPG）双层]或红细胞膜[中性棕榈酰油酰磷脂酰胆碱（POPC）/胆固醇双层]。从脂质到肽的H-1自旋扩散表明PG-1接触阴离子膜中的脂质酰基链和头基，但远离POPC/胆固醇双层中的脂质链。F-19自旋扩散数据表明，75%的p-发夹在阴离子膜中具有同源二聚化的N链和C链。所得到的（NCCN）（n）多聚体表明一个膜插入的β-桶包围一个水孔。β-桶周围的脂质具有高度的取向无序和链翻转，因此它们可以充当孔的填充物。这些结果修订的环形孔模型，首先提出magainin，随后应用到PG-1的几个功能。在POPC/胆固醇膜中，PG-1的N和C链聚簇成四聚体，表明在膜表面形成β-折叠。因此，膜组合物在限定PG-1的组装和插入中起决定性作用。PG-1的不同寡聚体结构有助于解释其对细菌的毒性大于对真核细胞的毒性。
We used solid-state NMR spectroscopy to investigate the oligomeric structure and insertion of protegrin-1 (PG-1), a beta-hairpin antimicrobial peptide, in lipid bilayers that mimic either the bacterial inner membrane [palmitoyloleoylphosphaticlyl ethanolamine and palmitoyloleoylphosphatidylglycerol (POPE/POPG) bilayers] or the red blood cell membrane [neutral palmitoyloleoylphosphatidylcholine (POPC)/cholesterol bilayers]. H-1 spin diffusion from lipids to the peptide indicates that PG-1 contacts both the lipid acyl chains and the headgroups in the anionic membrane but resides far from the lipid chains in the POPC/cholesterol bilayer. F-19 spin diffusion data indicates that 75% of the p-hairpins have homodimerized N strands and C strands in the anionic membrane. The resulting (NCCN)(n) multimer suggests a membrane-inserted beta-barrel enclosing a water pore. The lipids surrounding the beta-barrel have high orientational disorder and chain upturns, thus they may act as fillers for the pore. These results revise several features of the toroidal pore model, first proposed for magainin and subsequently applied to PG-1. In the POPC/cholesterol membrane, the N and C strands of PG-1 cluster into tetramers, suggesting the formation of beta-sheets on the membrane surface. Thus, the membrane composition plays a decisive role in defining the assembly and insertion of PG-1. The different oligomeric structures of PG-1 help to explain its greater toxicity for bacteria than for eukaryotic cells.