Native Mass Spectrometry of Antimicrobial Peptides in Lipid Nanodiscs Elucidates Complex Assembly
Native Mass Spectrometry of Antimicrobial Peptides in Lipid Nanodiscs Elucidates Complex Assembly
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DOI：
10.1021/acs.analchem.9b02261
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发表时间：
2019-07-16
影响因子：
7.4
通讯作者：
Marty, Michael T.
中科院分区：
文献类型：
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作者：
Walker, Lawrence R.;Marzluff, Elaine M.;Marty, Michael T.
抗菌肽（Antimicrobial peptides，AMP）是一类阳离子型的两亲性多肽，在对抗抗生素耐药性感染方面具有潜在的应用价值。已知AMP与细菌膜相互作用，但它们的毒性和选择性机制知之甚少，部分原因是表征脂质双层内的AMP寡聚复合物具有挑战性。在这里，我们使用天然质谱来测量插入具有不同脂质组分的脂蛋白纳米盘中的AMP的化学计量。增加肽浓度的滴定和碰撞活化实验表明，AMP可以表现出一系列行为，从非特异性掺入纳米盘到形成特异性复合物。这种表征脂质膜内AMP复合物形成的新方法将为AMP机制提供独特的见解。
Antimicrobial peptides (AMPs) are generally cationic and amphipathic peptides that show potential applications to combat the growing threat of antibiotic resistant infections. AMPs are known to interact with bacterial membranes, but their mechanisms of toxicity and selectivity are poorly understood, in part because it is challenging to characterize AMP oligomeric complexes within lipid bilayers. Here, we used native mass spectrometry to measure the stoichiometry of AMPs inserted into lipoprotein nanodiscs with different lipid components. Titrations of increasing peptide concentration and collisional activation experiments reveal that AMPs can exhibit a range of behaviors from nonspecific incorporation into the nanodisc to formation of specific complexes. This new approach to characterizing formation of AMP complexes within lipid membranes will provide unique insights into AMP mechanisms.