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Global Cell Surface Conformational Shift Mediated by a Candida albicans Adhesin

机译:念珠菌黏附素介导的全球细胞表面构象转变

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Candida albicans maintains both commensal and pathogenic states in humans. Both states are dependent on cell surface-expressed adhesins, including those of the Als family. Heterologous expression of Als5p at the surface of Saccharomyces cerevisiae results in Als5p-mediated adhesion to various ligands, followed by formation of multicellular aggregates. Following adhesion of one region of the cell to fibronectin-coated beads, the entire surface of the cells became competent to mediate cell-cell aggregation. Aggregates formed in the presence of metabolic inhibitors or signal transduction inhibitors but were reduced in the presence of 8-anilino-1-naphthalene-sulfonic acid (ANS) or Congo Red (CR), perturbants that inhibit protein structural transitions. These perturbants also inhibited aggregation of C. albicans. An increase in ANS fluorescence, which accompanied Als-dependent cellular adhesion, indicated an increase in cell surface hydrophobicity. In addition, C. albicans and Als5p-expressing S. cerevisiae showed an aggregation-induced birefringence indicative of order on the cell surface. The increase in birefringence did not occur in the presence of the aggregation disruptants ANS and CR. These results suggest a model for Als5p-mediated aggregation in which an adhesion-triggered change in the conformation of Als5p propagates around the cell surface, forming ordered aggregation-competent regions.
机译:白色念珠菌可维持人类的共鸣和致病状态。两种状态都依赖于细胞表面表达的粘附素,包括Als家族的粘附素。 Als5p在酿酒酵母表面的异源表达导致Als5p介导的对各种配体的粘附,随后形成多细胞聚集体。在将细胞的一个区域粘附到纤连蛋白包被的小球上之后,细胞的整个表面就能够介导细胞-细胞的聚集。聚集体在代谢抑制剂或信号转导抑制剂的存在下形成,但在抑制蛋白质结构转变的干扰物8-苯胺基-1-萘磺酸(ANS)或刚果红(CR)的存在下减少。这些干扰物也抑制了 C的聚集。白色的。 ANS荧光增加,伴随着Als依赖性细胞粘附,表明细胞表面疏水性增加。此外, C。白色念珠菌和表达Als5p的 S。啤酒酵母显示出聚集诱导的双折射,表明细胞表面有序。在存在聚集破坏剂ANS和CR的情况下,双折射没有增加。这些结果提示了Als5p介导的聚集模型,其中粘附触发的Als5p构象变化围绕细胞表面传播,形成有序的聚集能力区域。

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