The gamma-core motif correlates with antimicrobial activity in cysteine-containing kaliocin-1 originating from transferrins.
The gamma-core motif correlates with antimicrobial activity in cysteine-containing kaliocin-1 originating from transferrins.
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γ 核心基序与源自转铁蛋白的含半胱氨酸的 Kaliocin-1 的抗菌活性相关。
DOI：
10.1016/j.bbamem.2007.07.024
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发表时间：
2007
期刊：
影响因子：
--
通讯作者：
Yeaman,MichaelR
中科院分区：
文献类型：
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作者：
Yount,NannetteY;Andrés,MaríaT;Fierro,JoséF;Yeaman,MichaelR
钾霉素-1是一种31个残基的肽，来源于人乳铁蛋白，具有抗微生物特性，概括了其611个氨基酸的母体全蛋白。由于钾霉素-1是一种半胱氨酸稳定的肽，因此确定其是否含有最近鉴定为几乎所有类别的二硫键稳定的抗微生物肽所共有的多维γ-核心特征是有意义的。重要的是，序列和结构分析确定了钾霉素-1中这种多维抗菌特征的迭代。此外，发现γ-核心基序在整个系统发育谱中的转铁蛋白家族蛋白质中高度保守。先前的研究表明，钾霉素-1发挥抗念珠菌功效的机制取决于线粒体扰动而没有细胞膜透化。有趣的是，酵母双杂交筛选分析的结果确定了在酿酒酵母模型系统中钾霉素-1和线粒体起始因子2之间的相互作用。总之，这些数据扩展了含有γ-核心基序的抗微生物肽的库，并表明该基序在转铁蛋白家族蛋白的大的天然以及抗微生物肽亚组分内是保守的。最后，这些结果证实了与含有γ-核心基序的宿主防御效应蛋白相关的抗微生物活性可能对应于真菌线粒体或其细菌祖先共有的靶标的假设。
Kaliocin-1 is a 31-residue peptide derived from human lactoferrin, and with antimicrobial properties that recapitulate those of its 611 amino acid parent holoprotein. As kaliocin-1 is a cysteine-stabilized peptide, it was of interest to determine whether it contained a multidimensional γ-core signature recently identified as common to virtually all classes of disulfide-stabilized antimicrobial peptides. Importantly, sequence and structural analyses identified an iteration of this multidimensional antimicrobial signature in kaliocin-1. Further, the γ-core motif was found to be highly conserved in the transferrin family of proteins across the phylogenetic spectrum. Previous studies suggested that the mechanism by which kaliocin-1 exerts anti-candidal efficacy depends on mitochondrial perturbation without cell membrane permeabilization. Interestingly, results of a yeast two-hybrid screening analysis identified an interaction between kaliocin-1 and mitochondrial initiation factor 2 in a Saccharomyces cerevisiae model system. Taken together, these data extend the repertoire of antimicrobial peptides that contain γ-core motifs, and suggest that the motif is conserved within large native as well as antimicrobial peptide subcomponents of transferrin family proteins. Finally, these results substantiate the hypothesis that antimicrobial activity associated with host defense effector proteins containing a γ-core motif may correspond to targets common to fungal mitochondria or their bacterial ancestors.