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首页> 外文期刊>Journal of Molecular Biology >Heat shock protein 90 regulates development in Dictyostelium discoideum.
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Heat shock protein 90 regulates development in Dictyostelium discoideum.

机译：热激蛋白90调节盘基网柄菌的发育。

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摘要

Cytosolic heat shock protein 90 (Hsp90) has been implicated in diverse biological processes such as protein folding, cell cycle control, signal transduction, development, and morphological evolution. Model systems available for studying Hsp90 function either allow ease of manipulation for biochemical studies or facilitate a phenomenological study of its role in influencing phenotype. In this work, we have explored the use of the cellular slime mold Dictyostelium discoideum to examine cellular functions of Hsp90 in relation to its multicellular development. In addition to cloning, purification, biochemical characterization, and examination of its crystal structure, our studies, using a pharmacological inhibitor of Hsp90, demonstrate a role for the cytoplasmic isoform (HspD) in D. discoideum development. Inhibition of HspD function using geldanamycin (GA) resulted in delayed aggregation and arrest of D. discoideum development at the 'mound' stage. Crystal structure of the amino-terminal domain of HspD showed a binding pocket similar to that described for yeast Hsp90. Fluorescence spectroscopy, as well as GA-coupled beads affinity pulldown, confirmed a specific interaction between HspD and GA. The results presented here provide an important insight into the function of HspD in D. discoideum development and emphasize the potential of the cellular slime mold to serve as an effective model for studying the many roles of Hsp90 at cellular and organismal levels.
机译：胞质热休克蛋白90（Hsp90）与多种生物学过程有关，例如蛋白折叠，细胞周期控制，信号转导，发育和形态演变。可用于研究Hsp90功能的模型系统可简化生物化学研究的操作，或促进对其影响表型作用的现象学研究。在这项工作中，我们探索了使用细胞粘液霉菌盘基网柄菌来检查Hsp90与多细胞发育有关的细胞功能。除了克隆，纯化，生化特性及其晶体结构检查以外，我们的研究使用Hsp90的药理抑制剂，还证明了胞质亚型（HspD）在D. discoideum发育中的作用。使用格尔德霉素（GA）抑制HspD功能会导致在“丘”阶段D. discoideum发育的延迟聚集和停滞。 HspD氨基末端结构域的晶体结构显示出与酵母Hsp90相似的结合口袋。荧光光谱以及GA偶联的珠亲和力下拉，证实了HspD和GA之间的特定相互作用。此处提供的结果提供了对HspD在D. Discoideum发育中的功能的重要见解，并强调了细胞粘液霉菌作为研究Hsp90在细胞和机体水平的多种作用的有效模型的潜力。

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