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两株短小的、富含半胱氨酸和阳离子的抗真菌蛋白：青霉产黄青霉和青霉产黄菌素 B 的比较研究。

Two small, cysteine-rich and cationic antifungal proteins from Penicillium chrysogenum: A comparative study of PAF and PAFB.

机构信息

Institute of Molecular Biology, Biocenter, Medical University of Innsbruck, 6020 Innsbruck, Austria.

Institute of Plant Biology, Biological Research Centre, 6726 Szeged, Hungary; Department of Biotechnology, Faculty of Science and Informatics, University of Szeged, 6726 Szeged, Hungary.

出版信息

Biochim Biophys Acta Biomembr. 2020 Aug 1;1862(8):183246. doi: 10.1016/j.bbamem.2020.183246. Epub 2020 Mar 3.

DOI:10.1016/j.bbamem.2020.183246
PMID:32142818
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7138148/
Abstract

The filamentous fungus Penicillium chrysogenum Q176 secretes the antimicrobial proteins (AMPs) PAF and PAFB, which share a compact disulfide-bond mediated, β-fold structure rendering them highly stable. These two AMPs effectively inhibit the growth of human pathogenic fungi in micromolar concentrations and exhibit antiviral potential without causing cytotoxic effects on mammalian cells in vitro and in vivo. The antifungal mechanism of action of both AMPs is closely linked to - but not solely dependent on - the lipid composition of the fungal cell membrane and requires a strictly regulated protein uptake into the cell, indicating that PAF and PAFB are not canonical membrane active proteins. Variations in their antifungal spectrum and their killing dynamics point towards a divergent mode of action related to their physicochemical properties and surface charge distribution. In this review, we relate characteristic features of PAF and PAFB to the current knowledge about other AMPs of different sources. In addition, we present original data that have never been published before to substantiate our assumptions and provide evidences that help to explain and understand better the mechanistic function of PAF and PAFB. Finally, we underline the promising potential of PAF and PAFB as future antifungal therapeutics.

摘要

丝状真菌产黄青霉 Q176 分泌具有抗菌活性的蛋白质（AMPs）PAF 和 PAFB，它们具有紧密的二硫键介导的 β-折叠结构，使它们具有高度的稳定性。这两种 AMP 在微摩尔浓度下有效抑制人类致病真菌的生长，并表现出抗病毒潜力，而在体外和体内对哺乳动物细胞没有细胞毒性作用。两种 AMP 的抗真菌作用机制密切相关 - 但不仅依赖于 - 真菌细胞膜的脂质组成，并且需要严格调控蛋白质进入细胞，这表明 PAF 和 PAFB 不是典型的膜活性蛋白。它们在抗真菌谱和杀伤动力学方面的差异表明，与它们的物理化学性质和表面电荷分布相关的作用模式存在差异。在这篇综述中，我们将 PAF 和 PAFB 的特征与其他不同来源的 AMP 的现有知识联系起来。此外，我们还提供了以前从未发表过的原始数据，以证实我们的假设，并提供有助于更好地解释和理解 PAF 和 PAFB 的作用机制的证据。最后，我们强调了 PAF 和 PAFB 作为未来抗真菌治疗药物的有希望的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3fc/7138148/0cab425389bf/gr11_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3fc/7138148/b900813e7d1c/ga1_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3fc/7138148/ddddbe7a5925/gr1_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3fc/7138148/27c56f4cf5ca/gr2_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3fc/7138148/75642efd0b0c/gr3_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3fc/7138148/f3416ed09afe/gr4_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3fc/7138148/2738e05e8c75/gr5_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3fc/7138148/6064b19f3454/gr6_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3fc/7138148/d8ca1ba0bdeb/gr7_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3fc/7138148/67545961d016/gr8_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3fc/7138148/08e045aab793/gr9_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3fc/7138148/6cafd21dfc99/gr10_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3fc/7138148/0cab425389bf/gr11_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3fc/7138148/b900813e7d1c/ga1_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3fc/7138148/ddddbe7a5925/gr1_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3fc/7138148/27c56f4cf5ca/gr2_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3fc/7138148/75642efd0b0c/gr3_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3fc/7138148/f3416ed09afe/gr4_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3fc/7138148/2738e05e8c75/gr5_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3fc/7138148/6064b19f3454/gr6_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3fc/7138148/d8ca1ba0bdeb/gr7_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3fc/7138148/67545961d016/gr8_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3fc/7138148/08e045aab793/gr9_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3fc/7138148/6cafd21dfc99/gr10_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3fc/7138148/0cab425389bf/gr11_lrg.jpg

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