Domain structure, expressional regulation and autoimmunity of HSP90

应用异构体特异性的单抗，研究了HSP90两种异构体在大鼠不同组织和实验性磨牙移动过程中诱导的牙槽骨中破骨细胞和成骨细胞的表达。结果表明，热休克蛋白90β在大多数小鼠组织中的主要分布和组成分布以及应激诱导的热休克蛋白90α的表达。我们还研究了HtpG的结构域结构，HtpG是一种哺乳动物HSP90的大肠杆菌同源物，以及它的结构域间的相互作用。HtpG有Arg7-Gly8、Arg336-Glu337和Lys552-Leu553三个主要切割位点，对胰酶敏感。因此，HtpG由三个结构域组成：A结构域，METL-Arg336；B结构域，Glu337-Lys 552；C结构域，Leu553-Ser624。HtpG二聚体的结构域之间有三种相互作用：结构域B与结构域A和结构域C相互作用，而且结构域B有同源二聚体相互作用。结构域B和结构域C之间的相互作用决定了HtpG的二聚体构象。此外，B结构域在功能和结构上被分为两部分：与A结构域相互作用的N-末端三分之二(Glu337-Phe480)和与C结构域相互作用的C-末端三分之一(G1n481-Lys552)。这些特征似乎在HSP90家族成员蛋白中是常见的。

By use of isoform-specific monoclonal antibodies, the expression of the two HSP90 isoforms was investigated on various rat tissues and osteoclasts and osteoblasts that were induced in alveolar bones of the experimental movement of rat molar teeth. As a result, the predominant and constitutive distribution of HSP90β and stress-induced expression of HSP90α in most murine tissues were demonstrated. We also investigated the domain structure of HtpG, an Esherichia coli homologue of mammalian HSP90 and its domain-domain interactions. HtpG had three major cleavage sites, Arg7-Gly8, Arg336-Glu337 and Lys552-Leu553, susceptible to trypsin. Thus, HtpG consists of three domains: Domain A, Metl-Arg336; Domain B, Glu337-Lys 552; Domain C, Leu553-Ser624. Three kinds of interactions work between the domains of a HtpG dimer: Domain B interacted both with Domain A and Domain C, and moreover, Domain B had a homodimeric interaction. The interaction between Domain B and Domain C was responsible for the dimer conformation of HtpG. Furthermore, Domain B was functionally and structurally divided into two parts: the N-terminal two-third (Glu337-Phe480) that interacted with Domain A and the C-terminal one-third (G1n481-Lys552) that interacted with Domain C. This study first demonstrated the domain structure of HtpG and the interactions between the domains. These characteristics seem to be common among HSP90-family member proteins.