Lipid headgroup discrimination by antimicrobial peptide LL-37: Insight into mechanism of action
Lipid headgroup discrimination by antimicrobial peptide LL-37: Insight into mechanism of action
复制标题
DOI：
10.1529/biophysj.105.067595
复制
发表时间：
2006-02-01
影响因子：
3.4
通讯作者：
Gidalevitz, D
中科院分区：
文献类型：
--
作者：
Neville, F;Cahuzac, M;Gidalevitz, D
人抗菌肽LL-37与脂质单分子层的相互作用已经通过一系列补充技术进行了研究，包括压力-面积等温线，插入试验，落射荧光显微镜和同步辐射X-射线散射，以分析其作用机制。在空气-液体界面处形成脂质单层以模拟细菌细胞壁和外部莱亚的表面。用磷脂酰甘油（DPPG）、磷脂酰胆碱（DPPC）和磷脂酰乙醇胺（DPPE）脂质对红细胞膜进行了脂质体化。发现LL-37容易插入DPPG单层，破坏其结构，从而表明杀菌作用。相比之下，DPPC和DPPE单层几乎不受LL-37的影响，证明了其非溶血活性和脂质区分。镜面x射线反射率数据产生了相当大的差异，在层厚度和电子密度亲。在将肽加入DPPG单层后，但当探测由DPPC和DPPE组成的单层时，在肽注射后几乎没有观察到变化。掠入射X-射线衍射表明LL-37插入显著的肽插入和DPPG单层的侧向堆积顺序破坏。落射荧光显微镜数据支持这些发现。
Interaction of the human antimicrobial peptide LL-37 with lipid monolayers has been investigated by a range of complementary techniques including pressure-area isotherms, insertion assay, epifluorescence microscopy, and synchrotron x-ray scattering, to analyze its mechanism of action. Lipid monolayers were formed at the air-liquid interface to mimic the surface of the bacterial cell wall and the outer lea. et of erythrocyte cell membrane by using phosphatidylglycerol ( DPPG), phosphatidylcholine ( DPPC), and phosphatidylethanolamine ( DPPE) lipids. LL-37 is found to readily insert into DPPG monolayers, disrupting their structure and thus indicating bactericidal action. In contrast, DPPC and DPPE monolayers remained virtually unaffected by LL-37, demonstrating its nonhemolytic activity and lipid discrimination. Specular x-ray reflectivity data yielded considerable differences in layer thickness and electron-density pro. le after addition of the peptide to DPPG monolayers, but little change was seen after peptide injection when probing monolayers composed of DPPC and DPPE. Grazing incidence x-ray diffraction demonstrated significant peptide insertion and lateral packing order disruption of the DPPG monolayer by LL-37 insertion. Epifluorescence microscopy data support these findings.