Lee Michelle W, Lee Ernest Y, Ferguson Andrew L, Wong Gerard C L
Department of Bioengineering, Department of Chemistry, California NanoSystems Institute, University of California, Los Angeles, CA 90095, United States.
Institute for Molecular Engineering, University of Chicago, 5640 South Ellis Avenue, Chicago, IL 60637, United States.
Curr Opin Colloid Interface Sci. 2018 Nov;38:204-213. doi: 10.1016/j.cocis.2018.11.003. Epub 2018 Nov 16.
Antimicrobial peptides (AMPs) collectively constitute a key component of the host innate immune system. They span a diverse space of sequences and can be α-helical, β-sheet, or unfolded in structure. Despite a wealth of knowledge about them from decades of experiments, it remains difficult to articulate general principles governing such peptides. How are they different from other molecules that are also cationic and amphiphilic? What other functions, in immunity and otherwise, are enabled by these simple sequences? In this short review, we present some recent work that engages these questions using methods not usually applied to AMP studies, such as machine learning. We find that not only do AMP-like sequences confer membrane remodeling activity to an unexpectedly broad range of protein classes, their cationic and amphiphilic signature also allows them to act as meta-antigens and self-assemble with immune ligands into nanocrystalline complexes for multivalent presentation to Toll-like receptors.
抗菌肽（AMPs）共同构成宿主先天免疫系统的关键组成部分。它们的序列空间多样，结构上可以是α螺旋、β折叠或无规卷曲。尽管经过数十年的实验已积累了大量关于它们的知识，但仍难以阐明支配这类肽的一般原则。它们与其他同样带正电荷且具有两亲性的分子有何不同？这些简单序列在免疫及其他方面还具有哪些其他功能？在这篇简短的综述中，我们展示了一些近期的研究工作，这些工作运用了通常未应用于抗菌肽研究的方法，如机器学习，来探讨这些问题。我们发现，不仅类似抗菌肽的序列能赋予出乎意料的广泛蛋白质类别膜重塑活性，它们的阳离子和两亲性特征还使它们能够充当超抗原，并与免疫配体自组装成纳米晶体复合物，用于向Toll样受体进行多价呈递。
