Effect of Membrane Composition on Antimicrobial Peptides Aurein 2.2 and 2.3 From Australian Southern Bell Frogs
Effect of Membrane Composition on Antimicrobial Peptides Aurein 2.2 and 2.3 From Australian Southern Bell Frogs
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DOI：
10.1016/j.bpj.2008.10.012
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发表时间：
2009-01-21
影响因子：
3.4
通讯作者：
Straus, Suzana K.
中科院分区：
文献类型：
--
作者：
Cheng, John T. J.;Hale, John D.;Straus, Suzana K.
疏水厚度和摩尔磷脂酰甘油（PG）含量的脂质双层的结构和膜相互作用的三个阳离子抗菌肽的影响进行了研究：aurein 2.2，aurein 2.3（几乎相同的aurein 2.2，除了在残基13处的点突变），和羧基C-末端类似物aurein 2.3。圆二色性结果表明，在1，2-二肉豆蔻酰-sn-甘油基3-磷酸胆碱/1，2-二肉豆蔻酰-sn-甘油基-3-[磷酸-rac-（1-甘油）]的3：1摩尔混合物（DMPC/DMPG）和1-棕榈酰-2-油酰-sn-甘油基-3-磷酸胆碱/1-棕榈酰-2-油酰-sn-甘油基-3-[磷酸-rac-（1-甘油）]的1：1和3：1摩尔混合物（POPC/POPG）存在下，所有三种肽均采用α-螺旋结构。三种不同脂质组合物的定向圆二色谱数据表明，所有三种肽在低肽浓度下被表面吸附，但在较高肽浓度下被插入膜中。DMPC/DMPG和POPC/POPG双层膜中三种肽的（31）p固态NMR数据显示，所有三种肽均以肽或脂质组成依赖性方式显著扰动脂质头基。差示扫描量热分析结果表明，两种酰胺化金素肽对DMPC/DMPG双层膜的相结构都有一定的扰动，但对POPC/POPG链的扰动较小，DMPC/DMPG双层膜的扰动主要是胶束化，而POPC/POPG双层膜的扰动主要是扭曲的环形孔或局部膜聚集体的形成.钙黄绿素释放实验结果表明，金素肽在DMPC/DMPG脂质体中的膜渗漏比在POPC/POPG脂质体中严重，金素2.2在1：1和3：1的POPC/POPG脂质体中的钙黄绿素释放量高于金素2.3和金素2.3-COOH。最后，DiSC（3）5分析数据进一步将aurein 2.2与其他蛋白区分开来，表明它扰乱了完整S.金黄色葡萄球菌C622最有效，而金霉素2.3具有与短杆菌肽S相同的效率，并且金霉素2.3-COOH的效率最低。两者合计，这些数据表明，金素肽的膜相互作用的脂质双层的疏水厚度和PG含量的影响。
The effects of hydrophobic thickness and the molar phosphatidylglycerol (PG) content of lipid bilayers on the structure and membrane interaction of three cationic antimicrobial peptides were examined: aurein 2.2, aurein 2.3 (almost identical to aurein 2.2, except for a point mutation at residue 13), and a carboxy C-terminal analog of aurein 2.3. Circular dichroism results indicated that all three peptides adopt an a-helical structure in the presence of a 3:1 molar mixture of 1,2-dimyristoyi-sn-glycero3-phosphocholine/1,2-dimyristoyi-sn-glycero-3-[phospho-rac-(1-glycerol)] (DMPC/DMPG), and 1:1 and 3:1 molar mixtures of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine/1-paimitoyl-2-oleoyl-sn-glycero-3-[phospho-rac-(1-glycerol)] (POPC/POPG). Oriented circular dichroism data for three different lipid compositions showed that all three peptides were surface-adsorbed at low peptide concentrations, but were inserted into the membrane at higher peptide concentrations. The (31)p solid-state NMR data of the three peptides in the DMPC/DMPG and POPC/POPG bilayers showed that all three peptides significantly perturbed lipid headgroups, in a peptide or lipid composition-dependent manner. Differential scanning calorimetry results demonstrated that both amidated aurein peptides perturbed the overall phase structure of DMPC/DMPG bilayers, but perturbed the POPC/POPG chains less. The nature of the perturbation of DMPC/DMPG bilayers was most likely micellization, and for the POPC/POPG bilayers, distorted toroidal pores or localized membrane aggregate formation. Calcein release assay results showed that aurein peptide-induced membrane leakage was more severe in DMPC/DMPG liposomes than in POPC/POPG liposomes, and that aurein 2.2 induced higher calcein release than aurein 2.3 and aurein 2.3-COOH from 1:1 and 3:1 POPC/POPG liposomes. Finally, DiSC(3)5 assay data further delineated aurein 2.2 from the others by showing that it perturbed the lipid membranes of intact S. aureus C622 most efficiently, whereas aurein 2.3 had the same efficiency as gramicidin S, and aurein 2.3-COOH was the least efficient. Taken together, these data show that the membrane interactions of aurein peptides are affected by the hydrophobic thickness of the lipid bilayers and the PG content.