Biophysical Investigations Elucidating the Mechanisms of Action of Antimicrobial Peptides and Their Synergism.
Biophysical Investigations Elucidating the Mechanisms of Action of Antimicrobial Peptides and Their Synergism.
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DOI：
10.3390/biom8020018
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发表时间：
2018-04-18
期刊：
影响因子：
5.5
通讯作者：
Bechinger B
中科院分区：
文献类型：
--
作者：
Marquette A;Bechinger B
介绍了生物物理和结构方面的研究，重点是阳离子线性抗菌肽如Mainin、PGLa、LL37和蜂毒素的膜脂相互作用。用这些多肽进行的观察与用疏水性多肽丙氨蝶呤获得的数据是不同的。阳离子两亲性多肽主要采用平行于双层表面的膜排列，因此两亲性螺旋的极性和非极性侧链的分布反映了膜界面的环境变化。这种两亲性螺旋的膜分离已被证明在脂类堆积排列中引起相当大的破坏，在低肽浓度时瞬时打开，在较高的肽脂比时膜解体。脂类和多肽所采用的多种超分子排列方式由“软膜适应和响应，也是瞬时的”(SMART)模型表示。虽然分子动力学模拟提供了在抗菌肽存在的情况下脂膜的原子学观点，但生物物理研究在分子和超分子水平上揭示了有趣的细节，最近的显微成像实验描绘了细菌细胞接触抗菌肽时有趣的事件序列。最后，介绍了旨在揭示Mainin 2和PGLa协同作用机制的生物物理研究，包括未发表的等温滴定热法(ITC)、圆二色谱(CD)和动态光散射(DLS)测量，表明这些多肽通过介导膜间相互作用参与了脂质体的凝集。当两亲性多肽与膜表面平行排列时，一些结构事件被呈现在与两亲性多肽的抗菌和协同机制有关的示意性模型中。
Biophysical and structural investigations are presented with a focus on the membrane lipid interactions of cationic linear antibiotic peptides such as magainin, PGLa, LL37, and melittin. Observations made with these peptides are distinct as seen from data obtained with the hydrophobic peptide alamethicin. The cationic amphipathic peptides predominantly adopt membrane alignments parallel to the bilayer surface; thus the distribution of polar and non-polar side chains of the amphipathic helices mirror the environmental changes at the membrane interface. Such a membrane partitioning of an amphipathic helix has been shown to cause considerable disruptions in the lipid packing arrangements, transient openings at low peptide concentration, and membrane disintegration at higher peptide-to-lipid ratios. The manifold supramolecular arrangements adopted by lipids and peptides are represented by the ‘soft membranes adapt and respond, also transiently’ (SMART) model. Whereas molecular dynamics simulations provide atomistic views on lipid membranes in the presence of antimicrobial peptides, the biophysical investigations reveal interesting details on a molecular and supramolecular level, and recent microscopic imaging experiments delineate interesting sequences of events when bacterial cells are exposed to such peptides. Finally, biophysical studies that aim to reveal the mechanisms of synergistic interactions of magainin 2 and PGLa are presented, including unpublished isothermal titration calorimetry (ITC), circular dichroism (CD) and dynamic light scattering (DLS) measurements that suggest that the peptides are involved in liposome agglutination by mediating intermembrane interactions. A number of structural events are presented in schematic models that relate to the antimicrobial and synergistic mechanism of amphipathic peptides when they are aligned parallel to the membrane surface.
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影响因子：
4.6
作者：
Amos ST;Vermeer LS;Ferguson PM;Kozlowska J;Davy M;Bui TT;Drake AF;Lorenz CD;Mason AJ
通讯作者：
Mason AJ
影响因子：
5.6
作者：
Bechinger, B
通讯作者：
Bechinger, B
影响因子：
3.4
作者：
Bak, M;Bywater, RP;Nielsen, NC
通讯作者：
Nielsen, NC
影响因子：
0.7
作者：
Bolosov, I. A.;Kalashnikov, A. A.;Ovchinnikova, T. V.
通讯作者：
Ovchinnikova, T. V.
影响因子：
3.4
作者：
Barns, Kenneth J.;Weisshaar, James C.
通讯作者：
Weisshaar, James C.