Study on the structure and membrane disruption of the peptide oligomers constructed by hIAPP18-27 peptide and its d,l-alternating isomer.
Study on the structure and membrane disruption of the peptide oligomers constructed by hIAPP18-27 peptide and its d,l-alternating isomer.
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hIAPP18-27肽及其d,l-交替异构体构建的肽寡聚物的结构和膜破坏研究。
DOI：
10.1016/j.bbamem.2019.183108
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Fei Li
中科院分区：
文献类型：
--
作者：
Shuang Wang;Feihong Meng;Ruijie Hao;Chunyu Wang;Fei Li
越来越多的证据表明，淀粉样肽/蛋白质的寡聚中间体对生物膜是有毒的。然而，与破坏生物膜的能力密切相关的寡聚物的结构特征远未被理解。本研究利用hIAPP 18 - 27肽及其sd，l-交替异构体构建了两种寡聚体，通过渗漏实验和~（31）P NMR研究了寡聚体对POPC/POPG 4：1囊泡的破坏能力，并通过CD、TEM、~ 1H NMR和荧光猝灭实验表征了寡聚体的结构特征。我们发现，L-交替肽寡聚体比全L肽寡聚体对脂质膜的破坏性更大。二级结构的表征表明，该L-交替肽采用扩展的聚脯氨酸II型（PPII）构象，而全L肽在寡聚体中采用无规卷曲构象。与全L肽寡聚体相比，这些L-交替肽寡聚体不太紧凑，并且保持更多的疏水基团暴露于水。d，l-交替肽结构由PPII变为α-折叠，全L肽结构由无规卷曲变为β-折叠，这两种变化都降低了肽寡聚体破坏脂膜的能力。我们的研究结果表明，具有延长的肽链的寡聚体可能比具有折叠的肽链的寡聚体更有效地破坏膜，并且肽-肽相互作用的增加可能会降低寡聚体的破坏能力。
Increasing lines of evidence show that the oligomeric intermediates of amyloid peptides/proteins are toxic to biological membranes. However, the structural features of the oligomers that are closely associated with the ability to damage biological membranes are far from understanding. In this study, we constructed two species of oligomers using hIAPP18–27peptide and itsd,l-alternating isomer, examined the disruptive ability of the oligomers to POPC/POPG 4:1 vesicles by leakage assay and31P NMR spectroscopy, and characterized the structural features of the oligomers by CD, TEM,1H NMR and fluorescence quenching experiments. We found that thed,l-alternating peptide oligomers are more disruptive than the all-L peptide oligomers to the lipid membrane. The characterization of the secondary structure revealed that thed,l-alternating peptide adopts an extended polyproline type-II (PPII) conformation, while the all-L peptide adopts a random coil conformation in oligomers. Compared with the all-L peptide oligomers, thed,l-alternating peptide oligomers are less compact and keep more hydrophobic groups water exposed. Both the changes from PPII to α-sheet in the structure ofd,l-alternating peptide and from random coil to β-sheet in the structure of all-L peptide reduce the ability of the peptide oligomers to disrupt the lipid membrane. Our results suggest that an oligomer with extended peptide chains could be more potent in membrane disruption than an oligomer with folded peptide chains and an increase in peptide-peptide interaction could decrease the disruptive ability of oligomer.
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