Aggregation of cateslytin β-sheets on negatively charged lipids promotes rigid membrane domains.: A new mode of action for antimicrobial peptides?
Aggregation of cateslytin β-sheets on negatively charged lipids promotes rigid membrane domains.: A new mode of action for antimicrobial peptides?
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DOI：
10.1021/bi800448h
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发表时间：
2008-06-17
期刊：
影响因子：
2.9
通讯作者：
Dufourc, Erick J.
中科院分区：
文献类型：
--
作者：
Jean-Francois, Frantz;Castano, Sabine;Dufourc, Erick J.
Cateslytin是一种带正电荷的（5+）富含丝氨酸的抗菌肽（bCgA，RSMRLS-FRARGYGFR），是化学合成的，并针对模拟细菌或哺乳动物系统的膜进行了研究。圆二色谱，偏振衰减全反射红外光谱，H-1高分辨率MAS NMR，和H-2和P-31固态NMR被用来跟踪从肽和膜的观点的相互作用。Cateslytin在溶液中是非结构化的，其被转化成反平行的β-折叠，其在带负电荷的细菌模拟膜的表面上主要是平坦的聚集。精氨酸残基参与与带负电荷的脂质的结合。在cateslytin肽的相互作用之后，发现富含带负电荷的脂质的刚性和较厚的膜结构域：与中性哺乳动物模型膜检测到的相互作用少得多，如肽二级结构中仅少量百分比的β-折叠或螺旋所反映的。细菌和哺乳动物模型膜均未检测到膜破坏。提出了一种分子模型，其中不同的刚度和厚度的区域带来相边界缺陷，最终导致渗透性诱导和肽穿过细菌膜。
Cateslytin, a positively charged (5+) arginine-rich antimicrobial peptide (bCgA, RSMRLS-FRARGYGFR), was chemically synthesized and studied against membranes that mimic bacterial or mammalian systems. Circular dichroism, polarized attenuated total reflection infrared spectroscopy, H-1 high-resolution MAS NMR, and H-2 and P-31 solid state NMR were used to follow the interaction from peptide and membrane points of view. Cateslytin, which is unstructured in solution, is converted into antiparallel beta-sheets that aggregate mainly flat at the surface of negatively charged bacterial mimetic membranes. Arginine residues are involved in the binding to negatively charged lipids. Following the interaction of the cateslytin peptide, rigid and thicker membrane domains enriched in negatively charged lipids are found: Much less interaction is detected with neutral mammalian model membranes, as reflected by only minor percentages of beta-sheets or helices in the peptide secondary structure. No membrane destruction was detected for both bacterial and mammalian model membranes. A molecular model is proposed in which zones of different rigidity and thickness bring about phase boundary defects that ultimately lead to permeability induction and peptide crossing through bacterial membranes.