Effect of proline position on the antimicrobial mechanism of buforin II.
Effect of proline position on the antimicrobial mechanism of buforin II.
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DOI：
10.1016/j.peptides.2011.01.010
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发表时间：
2011-04
期刊：
影响因子：
3
通讯作者：
Elmore DE
中科院分区：
文献类型：
--
作者：
Xie Y;Fleming E;Chen JL;Elmore DE
Buforin II（BF 2）是一种组蛋白衍生的抗菌肽，通过跨膜转运并与核酸相互作用引起细胞死亡。它含有一个对其功能至关重要的脯氨酸残基。先前的研究发现，取代脯氨酸的突变导致膜转位和抗微生物活性降低以及膜透性增加。本研究通过改变脯氨酸的位置对膜转位、膜透性和抗菌活性的影响，进一步研究了脯氨酸在BF 2抗菌机制中的作用。为此目的，通过脯氨酸取代（P11A）或移位（P11A/G7 P、P11A/V12 P、P11A/V15 P）制备了四个突变体。这些突变改变了α-螺旋含量的量。虽然抗微生物活性与含脯氨酸的肽的α-螺旋含量相关，但膜移位不相关。这一观察结果表明，BF2的杀菌机制的因素，而不是易位必须改变这些突变。为了更好地解释这些趋势，我们还测量了突变肽的核酸结合和膜透化。突变体和野生型BF2活性的比较显示，BF2主要依赖于膜易位和核酸结合的抗微生物活性，虽然膜透化可能发挥一些BF2变体的次要作用。更好地理解脯氨酸在BF2抗菌机制中的作用将有助于BF2类似物的进一步设计和开发。此外，由于脯氨酸残基在其他抗菌肽中普遍存在，BF2的这种系统性表征提供了一般性的见解，可以促进我们对其他系统的理解。
Buforin II (BF2) is a histone-derived antimicrobial peptide that causes cell death by translocating across membranes and interacting with nucleic acids. It contains one proline residue critical for its function. Previous research found that mutations replacing proline lead to decreased membrane translocation and antimicrobial activity as well as increased membrane permeabilization. This study further investigates the role of proline in BF2’s antimicrobial mechanism by considering the effect of changing proline position on membrane translocation, membrane permeabilization, and antimicrobial activity. For this purpose, four mutants were made with proline substitution (P11A) or relocation (P11A/G7P, P11A/V12P, P11A/V15P). These mutations altered the amount of α-helical content. Although antimicrobial activity correlated with the α-helical content for the peptides containing proline, membrane translocation did not. This observation suggests that factors in BF2’s bactericidal mechanism other than translocation must be altered by these mutations. To better explain these trends we also measured the nucleic acid binding and membrane permeabilization of the mutant peptides. A comparison of mutant and wild type BF2 activity revealed that BF2 relies principally on membrane translocation and nucleic acid binding for antimicrobial activity, although membrane permeabilization may play a secondary role for some BF2 variants. A better understanding of the role of proline in the BF2 antimicrobial mechanism will contribute to the further design and development of BF2 analogues. Moreover, since proline residues are prevalent among other antimicrobial peptides, this systematic characterization of BF2 provides general insights that can promote our understanding of other systems.
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DOI：
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发表时间：
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影响因子：
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