Solution structure of a novel tryptophan-rich peptide with bidirectional antimicrobial activity
Solution structure of a novel tryptophan-rich peptide with bidirectional antimicrobial activity
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DOI：
10.1128/jb.188.1.328-334.2006
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发表时间：
2006-01-01
影响因子：
3.2
通讯作者：
Cheng, JW
中科院分区：
文献类型：
--
作者：
Wei, SY;Wu, JM;Cheng, JW
富含色氨酸的抗菌肽在许多植物、昆虫和哺乳动物的宿主先天防御机制中发挥重要作用。发现一种新型的富含Trp的肽Ac-KWRRWVRWI-NH 2（命名为Pac-525）对革兰氏阳性菌和革兰氏阴性菌都具有改善的活性。我们已经确定的溶液结构的PAC-525绑定到膜模拟十二烷基硫酸钠（SDS）胶束。Pac-525的SDS胶束结合结构在残基Trp 2、Arg 3和Arg 4处采用α-螺旋片段。带正电荷的残基聚集在一起形成亲水片。三个疏水残基Trp 2、Val 6和Ile 9形成疏水核心。表面静电势图表明三个色氨酸吲哚环紧靠肽骨架堆积并形成两亲性结构。此外，Pac-525的反向序列Ac-IWRVWRRWK-NH 2，命名为Pac-525（rev），在膜模拟胶束和囊泡中也显示出相似的抗微生物活性和结构。各种生物物理和生物化学方法，包括圆二色性，荧光光谱和微量热法，被用来显示，PAC-525强烈的相互作用与带负电荷的磷脂囊泡，并诱导有效的染料从这些囊泡释放，这表明PAC-525的抗菌活性可能是由于与细菌膜的相互作用。
Trp-rich antimicrobial peptides play important roles in the host innate defense mechanisms of many plants, insects, and mammals. A new type of Trp-rich peptide, Ac-KWRRWVRWI-NH2, designated Pac-525, was found to possess improved activity against both gram-positive and -negative bacteria. We have determined that the solution structures of Pac-525 bound to membrane-mimetic sodium dodecyl sulfate (SDS) micelles. The SDS micelle-bound structure of Pac-525 adopts an alpha-helical segment at residues Trp2, Arg3, and Arg4. The positively charged residues are clustered together to form a hydrophilic patch. The three hydrophobic residues Trp2, Val6, and Ile9 form a hydrophobic core. The surface electrostatic potential map indicates the three tryptophan indole rings are packed against the peptide backbone and form an amphipathic structure. Moreover, the reverse sequence of Pac-525, Ac-IWRVWRRWK-NH2, designated Pac-525(rev), also demonstrates similar antimicrobial activity and structure in membrane-mimetic micelles and vesicles. A variety of biophysical and biochemical methods, including circular dichroism, fluorescence spectroscopy, and microcalorimetry, were used to show that Pac-525 interacted strongly with negatively charged phospholipid vesicles and induced efficient dye release from these vesicles, suggesting that the antimicrobial activity of Pac-525 may be due to interactions with bacterial membranes.