Human antimicrobial peptides and proteins.
Human antimicrobial peptides and proteins.
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人类抗菌肽和蛋白质。
DOI：
10.3390/ph7050545
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发表时间：
2014-05-13
期刊：
影响因子：
--
通讯作者：
Wang G
中科院分区：
文献类型：
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作者：
Wang G
作为天然免疫的重要组成部分，人类宿主防御抗菌肽和蛋白（AMP）在抵御微生物病原体入侵方面发挥着重要作用。此外，AMP还具有其他生物学功能，如细胞凋亡、伤口愈合和免疫调节。本文综述了从抗菌肽数据库中筛选出的人抗菌肽的鉴定、活性、三维结构和作用机制。已经从各种组织和上皮表面，包括皮肤、眼睛、耳朵、口腔、肠道、免疫、神经和泌尿系统中鉴定出超过100种这样的肽。这些肽由10至150个氨基酸组成，净电荷在−3至+20之间，疏水含量低于60%。序列的多样性使得人类AMP能够采用不同的3D结构，并通过不同的机制攻击病原体。虽然α-防御素HD-6可以在细菌表面自组装成纳米网以缠绕细菌，但HNP-1和β-防御素hBD-3都能够通过结合脂质II来阻断细胞壁生物合成。溶菌酶的特征在于切割细菌细胞壁多糖，但也可以通过非催化机制杀死细菌。人凯萨林菌素LL-37的长的两亲性α-螺旋中的两个疏水结构域通过形成孔或经由地毯模型为结合和破坏弯曲的阴离子细菌膜表面奠定了基础。此外，杀皮素可通过形成长螺旋束结构而充当离子通道。此外，C型凝集素RegIIIα最初可以识别细菌肽聚糖，然后在膜中形成孔。最后，组胺素5和GAPDH（2-32）可以进入微生物细胞发挥作用。颗粒溶解素似乎在成孔穿孔素的帮助下进入细胞并杀死细胞内病原体。这种人类防御蛋白质的军火库不仅使我们保持健康，而且还激发了新一代个性化药物的开发，以对抗耐药性超级细菌，真菌，病毒，寄生虫或癌症。或者，多个因素（例如，白蛋白、精氨酸、丁酸盐、钙、环AMP、异亮氨酸、短链脂肪酸、UV B光、维生素D和锌）能够诱导抗微生物肽的表达，为抗感染药物的开发开辟了新的途径。
As the key components of innate immunity, human host defense antimicrobial peptides and proteins (AMPs) play a critical role in warding off invading microbial pathogens. In addition, AMPs can possess other biological functions such as apoptosis, wound healing, and immune modulation. This article provides an overview on the identification, activity, 3D structure, and mechanism of action of human AMPs selected from the antimicrobial peptide database. Over 100 such peptides have been identified from a variety of tissues and epithelial surfaces, including skin, eyes, ears, mouths, gut, immune, nervous and urinary systems. These peptides vary from 10 to 150 amino acids with a net charge between −3 and +20 and a hydrophobic content below 60%. The sequence diversity enables human AMPs to adopt various 3D structures and to attack pathogens by different mechanisms. While α-defensin HD-6 can self-assemble on the bacterial surface into nanonets to entangle bacteria, both HNP-1 and β-defensin hBD-3 are able to block cell wall biosynthesis by binding to lipid II. Lysozyme is well-characterized to cleave bacterial cell wall polysaccharides but can also kill bacteria by a non-catalytic mechanism. The two hydrophobic domains in the long amphipathic α-helix of human cathelicidin LL-37 lays the basis for binding and disrupting the curved anionic bacterial membrane surfaces by forming pores or via the carpet model. Furthermore, dermcidin may serve as ion channel by forming a long helix-bundle structure. In addition, the C-type lectin RegIIIα can initially recognize bacterial peptidoglycans followed by pore formation in the membrane. Finally, histatin 5 and GAPDH(2-32) can enter microbial cells to exert their effects. It appears that granulysin enters cells and kills intracellular pathogens with the aid of pore-forming perforin. This arsenal of human defense proteins not only keeps us healthy but also inspires the development of a new generation of personalized medicine to combat drug-resistant superbugs, fungi, viruses, parasites, or cancer. Alternatively, multiple factors (e.g., albumin, arginine, butyrate, calcium, cyclic AMP, isoleucine, short-chain fatty acids, UV B light, vitamin D, and zinc) are able to induce the expression of antimicrobial peptides, opening new avenues to the development of anti-infectious drugs.