中文摘要
热休克转录因子1 (HSF1)是HSF 中最典型、最具有代表性的。HSF1 从无DNA 结合的单体形式转换到有活性功能的三聚体的构象改变过程中，需要快速的与DNA 结合并特异性的结合到热休克启动因子而具有转录活性。热休克结合蛋白(HSBP1)是一个新近发现的含有两个伸展的疏水重复区，与HSF1 的三聚体区域以及HSP70 结合并相互作用。HSBP1 以其伴侣形式实现对HSF1 的DNA 结合活性有负调节作用，它通过抑制HSF1 与DNA 结合活性，从而抑制HSF1 的转录活性。本研究从对HSF1、HSBP1 以及HSF1-HSBP1 复合物的晶体结构测定入手，揭示HSF1 和HSBP1 相互作用机制以及二者在热休克反应过程中的调控机理。
英文摘要
Heat shock reaction is mainly regulated by the heat shock transcription factors(HSFs), of which HSF1 is a prototype. At the molecular level, most HSF proteins contain a conserved core region consisting of a DNA binding domain and a trimerization domain.Once activated, HSF uses its trimerization domain to form homo-trimers and translocates to nuclear where it exerts its transcription activator activity. For instance, in the absence of heat shock or other stresses, cytosol usually maintains certain level of HSP70 (or HSP90) which forms a complex with the inactive monomer form of HSF1 (HSF1-M) in mammalian cells, the up-regulated HSP70 may bind with HSF1-M to inhibit the formation of active HSF1-T, thus forming a negative feed-back pathway.Using either the full length or trimerization domain of HSF1 as the bait, a protein termed heat shock binding protein 1 (HSBP1) was identified in a yeast-two-hybridization analysis and subsequently characterized.The discovery of HSBP1 advanced our understanding of the HSF regulation pathway. At the initial stage of HSR, HSBP1-HSF1-T complex can be observed.To understand the structural basis of HSF1 regulation by HSBP1,we carried out structural studies on these key proteins in HSR. So we study on the crystal structure of the HSBP1 ,HSF1 and the complex of HSBP1-HSF1 to illuminate the regulation mechanism of HSR.
结题摘要
热休克转录因子1 (HSF1)是HSF 中最典型、最具有代表性的。HSF1 从无DNA 结合的单体形式转换到有活性功能的三聚体的构象改变过程中，需要快速的与DNA 结合并特异性的结合到热休克启动因子而具有转录活性。热休克结合蛋白(HSBP1)是一个新近发现的含有两个伸展的疏水重复区，与HSF1 的三聚体区域以及HSP70 结合并相互作用。HSBP1 以其伴侣形式实现对HSF1 的DNA 结合活性有负调节作用，它通过抑制HSF1 与DNA 结合活性，从而抑制HSF1 的转录活性。本研究从对HSF1、HSBP1 以及HSF1-HSBP1 复合物的晶体结构测定入手，揭示HSF1 和HSBP1 相互作用机制以及二者在热休克反应过程中的调控机理。