High-quality 3D structures shine light on antibacterial, anti-biofilm and antiviral activities of human cathelicidin LL-37 and its fragments.
High-quality 3D structures shine light on antibacterial, anti-biofilm and antiviral activities of human cathelicidin LL-37 and its fragments.
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DOI：
10.1016/j.bbamem.2014.01.016
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发表时间：
2014-09
影响因子：
3.4
通讯作者：
Epand, Richard M.
中科院分区：
文献类型：
--
作者：
Wang, Guangshun;Mishra, Biswajit;Epand, Raquel F.;Epand, Richard M.
宿主防御抗菌肽是人体先天免疫的重要组成部分，在人体健康中起着不可缺少的作用。虽然在马、牛、猪和羊身上都有多个抗菌肽基因拷贝，但在人类身上只发现了一个抗菌肽基因。有趣的是，这个单一的抗菌肽基因可以被加工成不同形式的抗菌肽。LL-37是最常见的研究形式，它不仅具有抗菌作用，还具有趋化、细胞凋亡、伤口愈合、免疫调节和癌症转移等功能。本文综述了人LL-37及其片段在结构和生物物理方面的研究进展，为进一步了解其抗菌、抗生物膜和抗病毒活性提供基础。利用改进的二维核磁共振方法对肽片段和三维核磁共振光谱对完整的LL-37进行了高质量的结构。LL-37的长两亲螺旋（残基2-31）中的两个疏水结构域被亲水性残基丝氨酸9隔开，这解释了它与细菌脂多糖（LPS）的协同结合。LL-37的芳香环（F5、F6、F17和F27）和界面碱性氨基酸直接与阴离子型磷脂酰甘油（PG）相互作用。尽管文献中报道的肽序列略有不同，但一致认为LL-37的中心螺旋对于破坏超级细菌（例如MRSA），细菌生物膜以及人类免疫缺陷病毒1 （HIV-1）和呼吸道合胞病毒（RSV）等病毒至关重要。在中央螺旋中，中央精氨酸R23在结合细菌膜或DNA方面起着特别重要的作用。绘制LL-37主要抗菌区域阳离子氨基酸的功能作用图谱，为设计具有理想性能的抗菌肽提供了基础。
Host defense antimicrobial peptides are key components of human innate immunity that plays an indispensible role in human health. While there are multiple copies of cathelicidin genes in horses, cattle, pigs, and sheep, only one cathelicidin gene is found in humans. Interestingly, this single cathelicidin gene can be processed into different forms of antimicrobial peptides. LL-37, the most commonly studied form, is not only antimicrobial but also possesses other functional roles such as chemotaxis, apoptosis, wound healing, immune modulation, and cancer metastasis. This article reviews recent advances made in structural and biophysical studies of human LL-37 and its fragments, which serve as a basis to understand their antibacterial, anti-biofilm and antiviral activities. High-quality structures were made possible by using improved 2D NMR methods for peptide fragments and 3D NMR spectroscopy for intact LL-37. The two hydrophobic domains in the long amphipathic helix (residues 2-31) of LL-37 separated by a hydrophilic residue serine 9 explain its cooperative binding to bacterial lipopolysaccharides (LPS). Both aromatic rings (F5, F6, F17, and F27) and interfacial basic amino acids of LL-37 directly interact with anionic phosphatidylglycerols (PG). Although the peptide sequences reported in the literature vary slightly, there is a consensus that the central helix of LL-37 is essential for disrupting superbugs (e.g., MRSA), bacterial biofilms, and viruses such as human immunodeficiency virus 1 (HIV-1) and respiratory syncytial virus (RSV). In the central helix, the central arginine R23 is of particular importance in binding to bacterial membranes or DNA. Mapping the functional roles of the cationic amino acids of the major antimicrobial region of LL-37 provides a basis for designing antimicrobial peptides with desired properties.
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影响因子：
3.7
作者：
Currie SM;Findlay EG;McHugh BJ;Mackellar A;Man T;Macmillan D;Wang H;Fitch PM;Schwarze J;Davidson DJ
通讯作者：
Davidson DJ
影响因子：
2.1
作者：
Epand, Richard M.;Epand, Raquel F.
通讯作者：
Epand, Raquel F.
影响因子：
4.9
作者：
Epand, Raquel F.;Wang, Guangshun;Epand, Richard M.
通讯作者：
Epand, Richard M.
影响因子：
3.7
作者：
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通讯作者：
Donis RO
影响因子：
4.2
作者：
Dean SN;Bishop BM;van Hoek ML
通讯作者：
van Hoek ML