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首页> 外文期刊>Biochemistry >Structural features responsible for the biological stability of Histoplasma's virulence factor CBP
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Structural features responsible for the biological stability of Histoplasma's virulence factor CBP

机译：负责组织胞浆毒力因子CBP生物学稳定性的结构特征

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摘要

The virulence factor CBP is the most abundant protein secreted by Histoplasma capsulatum, a pathogenic fungus that causes histoplasmosis. Although the biochemical function and pathogenic mechanism of CBP are unknown, quantitative Ca2+ binding measurements indicate that CBP has a strong affinity for calcium (K-D = 6.45 +/- 0.4 nM). However, no change in structure was observed upon binding of calcium, prompting a more thorough investigation of the molecular properties of CBP with respect to self-association, secondary structure, and stability. Over a wide range of pH values and salt concentrations, CBP exists predominantly as a stable, noncovalent homodimer in both its calcium-free and -bound states. Solution-state NMR and circular dichroism (CD) measurements indicated that the protein is largely cc-helical, and its secondary structure content changes little over the range of pH values encountered physiologically. ESI-MS revealed that the six cysteine residues of CBP are involved in three intramolecular disulfide bonds that help maintain a highly protease resistant structure. Thermally and chemically induced denaturation studies indicated that unfolding of disulfide-intact CBP is reversible and provided quantitative measurements of protein stability. This disulfide-linked, protease resistant, homodimeric a-helical structure of CBP is likely to be advantageous for a virulence factor that must Survive the harsh environment within the phagolysosomes of host macrophages.
机译：毒力因子CBP是荚膜组织胞浆菌（一种引起组织胞浆菌病的致病真菌）分泌的最丰富的蛋白质。尽管尚不清楚CBP的生化功能和致病机理，但定量的Ca2 +结合测量表明CBP对钙具有很强的亲和力（K-D = 6.45 +/- 0.4 nM）。然而，在钙结合时未观察到结构变化，从而促使人们对CBP的分子性质进行更彻底的研究，包括自缔合，二级结构和稳定性。在很宽的pH值和盐浓度范围内，CBP主要以稳定的，非共价的同二聚体形式存在，既无钙又有结合状态。溶液状态的NMR和圆二色性（CD）测量表明该蛋白质主要为cc螺旋，其二级结构含量在生理上遇到的pH值范围内几乎没有变化。 ESI-MS显示CBP的六个半胱氨酸残基与三个分子内二硫键有关，有助于维持高度蛋白酶抗性结构。热和化学诱导的变性研究表明，完整的二硫键CBP的展开是可逆的，并提供了蛋白质稳定性的定量测量。 CBP的这种二硫键连接的，蛋白酶抗性的，同二聚的a螺旋结构可能对于必须在宿主巨噬细胞的吞噬溶酶体中生存的恶劣环境的毒力因子有利。

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