FURTHER ELUCIDATION OF THE INTEREACTIONS IN THE MULTICHAPERONE-HAP1 COMPLEXES

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 酵母中的氧感应和血红素信号转导涉及转录调控因子Hap1和分子伴侣蛋白，包括Hsp90和SSA(Hsp70)及其伴侣蛋白。血红素调节Hap1的转录活性，这种调节涉及到一个多伴侣复合体的形成。Hap1不断地被SSA及其辅伴侣结合，维持Hap1的抑制状态。Hap1似乎只与Hsp90短暂结合，而血红素浓度的增加加强了这种相互作用。为了进一步了解Hap1和伴侣之间的空间关系，并确定对Hap1-多伴侣复合体的形成至关重要的结构域，我们将利用多种方法，包括FRET成像分析。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Oxygen sensing and heme signaling in yeast involve the actions of the transcriptional regulator Hap1 and molecular chaperones, including Hsp90 and Ssa (Hsp70) and their chaperones. Heme regulates Hap1 transcriptional activity, and this regulation involves the formation of a multichaperone complex. Hap1 is continuously bound by Ssa and its cochaperones, maintaining Hap1 in its repressed state. Hap1 appears to be bound to Hsp90 only transiently, and increases in heme concentration enhance this interaction. To further understand the spatial relationship between Hap1 and chaperones and to determine the domains that are important for the formation of Hap1-multichaperone complexes, we will utilize multiple approaches, including FRET imaging analysis.