C-末端酰胺化在抗菌肽aurein 1.2作用机制中的作用

IF 1.2 Q3 MULTIDISCIPLINARY SCIENCES
M. Shahmiri, A. Mechler
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引用次数: 10

摘要

摘要C-末端酰胺化是野生型破膜抗菌肽(AMP)的一个常见特征。经验证据表明,这种修饰提高了抗菌效果。然而,C末端酰胺化在AMPs作用的分子机制中的实际作用尚不完全清楚。酰胺化同时改变了两个关键特性:肽的净电荷和螺旋度,这两个特性都与作用机制有关。然而,在以前的研究中,羧基和酰胺部分的物理化学性质之间的差异被忽略了。在这项研究中,我们评估了活性的差异是否只是由肽的螺旋度和总电荷的变化引起的,即末端的化学性质是否在其他方面无关。为此,研究了修饰的aurein 1.2肽的膜破坏活性,其中用末端甲基形成仲酰胺,而不是野生型肽中的伯酰胺。石英晶体微量天平、染料渗漏和圆二色性实验的结果表明,与野生型肽相比,修饰肽的活性显著降低,特别是修饰肽与膜结合的能力大大降低。因此,C末端的伯酰胺需要与膜结合,而仲酰胺不能起到相同的作用。我们假设这种差异与末端的水合状态有关。修饰肽的膜结合能力的缺乏将C末端的伯酰胺部分鉴定为特定的膜结合基序。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
The role of C-terminal amidation in the mechanism of action of the antimicrobial peptide aurein 1.2
Abstract C-terminal amidation is a common feature of wild type membrane disrupting antimicrobial peptides (AMPs). Empirical evidence suggests that this modification increases antimicrobial efficacy. However, the actual role of C-terminal amidation in the molecular mechanism of action of AMPs is not fully understood. Amidation alters two key properties simultaneously: the net charge and helicity of the peptide, both of which are implicated in the mechanism of action. However, the differences between the physicochemical properties of the carboxyl and amide moieties have been disregarded in former studies. In this study we assessed whether the difference in activity is only caused by changes in the helicity and overall charge of a peptide, i.e. whether the chemistry of the terminus is otherwise irrelevant. To do so, the membrane disrupting activity of a modified aurein 1.2 peptide was studied in which a secondary amide was formed with a terminal methyl group, instead of the primary amide as in the wild type peptide. Results of quartz crystal microbalance, dye leakage and circular dichroism experiments show that the activity of the modified peptide is substantially reduced compared to the wild type peptide, in particular that the modified peptide exhibited a much-reduced ability to bind to the membrane. Thus, the primary amide at the C-terminus is required to bind to the membrane, and a secondary amide cannot serve the same purpose. We hypothesize that this difference is related to the hydration state of the terminus. The lack of membrane binding ability of the modified peptide identifies the primary amide moiety at the C terminus as a specific membrane binding motif.
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来源期刊
The EuroBiotech Journal
The EuroBiotech Journal Agricultural and Biological Sciences-Food Science
CiteScore
3.60
自引率
0.00%
发文量
17
审稿时长
10 weeks
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