Biophysical investigation of the membrane-disrupting mechanism of the antimicrobial and amyloid-like peptide dermaseptin S9.
Biophysical investigation of the membrane-disrupting mechanism of the antimicrobial and amyloid-like peptide dermaseptin S9.
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DOI：
10.1371/journal.pone.0075528
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Khemtémourian L
中科院分区：
文献类型：
--
作者：
Caillon L;Killian JA;Lequin O;Khemtémourian L
Dermaseptin S9（Drs S9）是一种非典型的阳离子抗菌肽，具有长的疏水核心，并具有形成淀粉样原纤维的倾向。在这里，我们研究了它的膜相互作用，使用各种生物物理技术。相当令人惊讶的是，我们发现Drs S9在两性离子磷脂酰胆碱（PC）囊泡中诱导有效的透化，但在阴离子磷脂酰甘油（PG）囊泡中不诱导。我们还发现，肽插入更有效地在PC比PG单层。因此，阳离子Drs S9和阴离子膜之间的静电相互作用不能解释肽对细菌膜的选择性。CD光谱、电子显微镜和ThT荧光实验表明，与PG膜相比，在PC膜存在下，肽采用略微更多的β-折叠，并且具有更高的形成淀粉样原纤维的倾向。因此，渗漏的诱导可能与肽聚集有关。使用预掺入方案减少溶液中聚集体的肽/肽相互作用特征，导致更多α-螺旋形成，并对所有检测的脂质系统中凝胶-流体脂质相变的协同性产生更显著的影响。量热数据与2 H-和31 P-NMR实验表明，肽的动态组织的脂质双层有显着的影响，虽然略低于两性离子比阴离子膜。总之，我们的数据表明，特别是在两性离子脂质膜中，肽以聚集状态结合，导致膜渗漏。我们提出，Drs S9的抗微生物活性也可能是肽在聚集状态下结合的结果，但是与细菌膜的特异性结合和聚集不是由阴离子脂质而是由未知因素调节的。
Dermaseptin S9 (Drs S9) is an atypical cationic antimicrobial peptide with a long hydrophobic core and with a propensity to form amyloid-like fibrils. Here we investigated its membrane interaction using a variety of biophysical techniques. Rather surprisingly, we found that Drs S9 induces efficient permeabilisation in zwitterionic phosphatidylcholine (PC) vesicles, but not in anionic phosphatidylglycerol (PG) vesicles. We also found that the peptide inserts more efficiently in PC than in PG monolayers. Therefore, electrostatic interactions between the cationic Drs S9 and anionic membranes cannot explain the selectivity of the peptide towards bacterial membranes. CD spectroscopy, electron microscopy and ThT fluorescence experiments showed that the peptide adopts slightly more β-sheet and has a higher tendency to form amyloid-like fibrils in the presence of PC membranes as compared to PG membranes. Thus, induction of leakage may be related to peptide aggregation. The use of a pre-incorporation protocol to reduce peptide/peptide interactions characteristic of aggregates in solution resulted in more α-helix formation and a more pronounced effect on the cooperativity of the gel-fluid lipid phase transition in all lipid systems tested. Calorimetric data together with 2H- and 31P-NMR experiments indicated that the peptide has a significant impact on the dynamic organization of lipid bilayers, albeit slightly less for zwitterionic than for anionic membranes. Taken together, our data suggest that in particular in membranes of zwitterionic lipids the peptide binds in an aggregated state resulting in membrane leakage. We propose that also the antimicrobial activity of Drs S9 may be a result of binding of the peptide in an aggregated state, but that specific binding and aggregation to bacterial membranes is regulated not by anionic lipids but by as yet unknown factors.
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DOI：
10.1016/0005-2736(75)90045-0
发表时间：
1975-01-01
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA
影响因子：
--
作者：
DEMEL, RA;GEURTSVANKESSEL, WSM;VANDEENEN, LLM
通讯作者：
VANDEENEN, LLM
影响因子：
2.7
作者：
Byrne, Cillian;Khemtemourian, Lucie;Jacquot, Yves
通讯作者：
Jacquot, Yves
影响因子：
3.4
作者：
Castano, S;Desbat, B;Dufourcq, J
通讯作者：
Dufourcq, J
影响因子：
3.4
作者：
Joanne, Pierre;Galanth, Cecile;Alves, Isabel D.
通讯作者：
Alves, Isabel D.
影响因子：
5.4
作者：
Auvynet, Constance;El Amri, Chahrazade;Rosenstein, Yvonne
通讯作者：
Rosenstein, Yvonne