Domain structure, expressional regulation and autoimmunity of HSP90

利用同种异构体特异性单克隆抗体，研究了两种HSP90同种异构体在大鼠磨牙实验运动牙槽骨诱导的各种组织及破骨细胞和成骨细胞中的表达。结果表明，HSP90β和应激诱导的HSP90α在大多数小鼠组织中具有优势和组成性分布。我们还研究了哺乳动物HSP90的大肠杆菌同源物HtpG的结构域结构及其结构域相互作用。HtpG有3个对胰蛋白酶敏感的主要切割位点Arg7-Gly8、Arg336-Glu337和Lys552-Leu553。因此，HtpG由三个结构域组成：结构域A， metal - arg336；结构域B， Glu337-Lys 552；结构域C， Leu553-Ser624。HtpG二聚体结构域之间存在三种相互作用：结构域B与结构域a和结构域C相互作用，结构域B具有同二聚体相互作用。结构域B和结构域C之间的相互作用是HtpG二聚体构象的主要原因。此外，结构域B在功能和结构上被分为两部分：与结构域A相互作用的n端2 / 3 （Glu337-Phe480）和与结构域c相互作用的c端1 / 3 （G1n481-Lys552）。本研究首次证明了HtpG结构域的结构和结构域之间的相互作用。这些特征似乎在hsp90家族成员蛋白中是共同的。

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.