Functional determinants of a synthetic vesicle fusion system

Functional determinants of a synthetic vesicle fusion system
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DOI:
10.1021/ja711184u
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发表时间:
2008-05-14
影响因子:
15
通讯作者:
Bong, Dennis
Bong, Dennis
中科院分区:
化学1区
文献类型:
--
作者:
Gong, Yun;Ma, Mingming;Bong, Dennis

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选择性膜合并可能是由合成的表面展示的融合子之间的小分子识别驱动的,所述融合子携带万古霉素糖肽和其天然结合靶标D-Ala-D-Ala二肽。这些识别基序分别由抗菌肽爪蟾抗菌肽II和磷脂酰乙醇胺脂质衍生物膜锚定。我们在此报告的合成膜融合反应的表征方面如下:融合剂浓度的影响,脂质组合物,和膜电荷。我们的研究结果表明,这些参数的融合率,囊泡稳定性,肽结合,催化融合和融合过程中的膜破坏的决定因素。值得注意的是,这些数据表明分子识别和插入的双层激活之间的耦合的重要性,以及膜融合反应性的膜子域形成的关键作用。这些现象是一般的脂质膜化学,因此这些发现提供了一个指导方针,了解更复杂的生物膜系统。
Selective membrane mergers may be driven by small-molecule recognition between synthetic surface-displayed fusogens which bear vancomycin glycopeptide and its native binding target, D-Ala-D-Ala dipeptide. These recognition motifs are membrane anchored by antimicrobial peptide magainin II and a phosphatidylethanolamine lipid derivative, respectively. We report herein characterization of this synthetic membrane fusion reaction with regard to the following: effects of fusogen concentration, lipid composition, and membrane charge. Our findings indicate that these parameters are determinants of fusion rate, vesicle stability, peptide binding, catalytic fusion and membrane disruption during fusion. Notably, these data indicate the importance of coupling between molecular recognition and insertion for bilayer activation as well as the critical role of membrane subdomain formation for membrane fusion reactivity. These phenomena are general to lipid membrane chemistry, and therefore these findings provide a guideline for understanding more complex biomembrane systems.