Candida albicans Als adhesins have conserved amyloid-forming sequences
Candida albicans Als adhesins have conserved amyloid-forming sequences
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DOI：
10.1128/ec.00309-07
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发表时间：
2008-05-01
期刊：
影响因子：
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通讯作者：
Lipke, Peter N.
中科院分区：
文献类型：
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作者：
Otoo, Henry N.;Lee, Kyeng Gea;Lipke, Peter N.
白念珠菌细胞壁结合的ALS粘附素调节酵母对宿主组织的黏附和酵母菌的聚集。这种聚集是淀粉样的，具有自传播的二级结构变化，淀粉样特征的染料结合，以及诱导的双折射(J.M.Ruceo，N.K.Gaur，K.G.Lee，J.E.Edwards，S.A.Klotz和P.N.Lipke，Infect。伊蒙。72：4948-4955,2004)。因此，我们确定了Als蛋白是否可以形成具有细胞聚集特性的淀粉样纤维。β聚集预测因子Tango确定了Als1p、Als3p和Als5p中存在高度保守序列的七肽序列，具有淀粉样蛋白形成潜力。含有该序列的十三肽形成了结合刚果红和硫代黄素T的纤维，并具有特征性的淀粉样蛋白形态。Als5p(20-431)和Als5p(20-664)是含有淀粉样蛋白序列的Als5p大片段，在自然条件下也形成了淀粉样纤维并与刚果红结合。K-a/K-S分析表明，淀粉样蛋白的形成序列在ALS蛋白中高度保守，并且比蛋白质的其他区域进化得更慢。因此，淀粉样蛋白的形成能力本身在这些蛋白质中是保守的。
The cell wall-bound Als adhesins of Candida albicans mediate both yeast-to-host tissue adherence and yeast aggregation. This aggregation is amyloid-like, with self-propagating secondary-structure changes, amyloid-characteristic dye binding, and induced birefringence (J. M. Rauceo, N. K. Gaur, K. G. Lee, J. E. Edwards, S. A. Klotz, and P. N. Lipke, Infect. Immun. 72: 4948-4955, 2004). Therefore, we determined whether Als proteins could form amyloid fibers with properties like those in cellular aggregation. The beta-aggregation predictor TANGO identified a heptapeptide sequence present in a highly conserved sequence with amyloid-forming potential in Als1p, Als3p, and Als5p. A tridecapeptide containing this sequence formed fibers that bound Congo red and thioflavin T and had characteristic amyloid morphology. Als5p(20-431) and Als5p(20-664), large fragments of Als5p containing the amyloid sequence, also formed amyloid-like fibers and bound Congo red under native conditions. K-a/K-s analysis showed that the amyloid-forming sequences are highly conserved in Als proteins and evolve more slowly than other regions of the proteins. Therefore, amyloid-forming ability itself is conserved in these proteins.