Molecular architecture of fungal cell walls revealed by solid-state NMR.
Molecular architecture of fungal cell walls revealed by solid-state NMR.
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DOI：
10.1038/s41467-018-05199-0
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发表时间：
2018-07-16
影响因子：
16.6
通讯作者：
Wang T
中科院分区：
文献类型：
--
作者：
Kang X;Kirui A;Muszyński A;Widanage MCD;Chen A;Azadi P;Wang P;Mentink-Vigier F;Wang T
侵袭性真菌感染的高死亡率，以及抗真菌药物的有限数量和无效性，需要开发具有新机制和靶点的新药物。真菌细胞壁是一个有前途的目标，因为它含有人类中不存在的多糖，然而，其分子结构仍然难以捉摸。在这里，我们报告的建筑细胞壁的致病真菌烟曲霉。在动态核极化和糖基键分析的辅助下，固态核磁共振光谱表明，甲壳素和α-1，3-葡聚糖构建了一个疏水性支架，该支架被不同连接的β-葡聚糖的水合基质包围，并被糖蛋白的动态层覆盖。和α-1，3-葡聚糖。α-1，3-葡聚糖的双结构域分布表明该分子具有双重功能：有助于细胞壁刚性和真菌毒力。这项研究提供了一个高分辨率的真菌细胞壁模型，并作为评估药物反应的基础，以促进壁靶向抗真菌药物的发展。烟曲霉是一种致病真菌。在这里，作者对完整的曲霉细胞进行了固态核磁共振测量，这提供了对细胞壁组成和动力学的见解，并提出了真菌细胞壁的结构模型。
The high mortality of invasive fungal infections, and the limited number and inefficacy of antifungals necessitate the development of new agents with novel mechanisms and targets. The fungal cell wall is a promising target as it contains polysaccharides absent in humans, however, its molecular structure remains elusive. Here we report the architecture of the cell walls in the pathogenic fungus Aspergillus fumigatus. Solid-state NMR spectroscopy, assisted by dynamic nuclear polarization and glycosyl linkage analysis, reveals that chitin and α-1,3-glucan build a hydrophobic scaffold that is surrounded by a hydrated matrix of diversely linked β-glucans and capped by a dynamic layer of glycoproteins and α-1,3-glucan. The two-domain distribution of α-1,3-glucans signifies the dual functions of this molecule: contributing to cell wall rigidity and fungal virulence. This study provides a high-resolution model of fungal cell walls and serves as the basis for assessing drug response to promote the development of wall-targeted antifungals. Aspergillus fumigatus is a pathogenic fungus. Here the authors perform solid-state NMR measurements with intact Aspergillus cells, which provides insights into cell wall composition and dynamics and propose a structural model for fungal cell walls.
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