FURTHER ELUCIDATION OF THE INTEREACTIONS IN THE MULTICHAPERONE-HAP1 COMPLEXES

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 酵母中的氧传感和血红素信号传导涉及转录调节因子Hap 1和分子伴侣的作用，包括Hsp 90和Ssa（Hsp 70）及其伴侣。 血红素调节Hap 1的转录活性，这种调节涉及多分子伴侣复合物的形成。 Hap 1被Ssa及其辅伴侣持续结合，维持Hap 1处于其抑制状态。 Hap 1似乎只能短暂地与Hsp 90结合，血红素浓度的增加增强了这种相互作用。 为了进一步了解Hap 1和分子伴侣之间的空间关系，并确定对Hap 1-multichaperone复合物的形成很重要的结构域，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.