Wiech H, Buchner J, Zimmermann M, Zimmermann R, Jakob U
Zentrum Biochemie/Abteilung Biochemie II, Universität Göttingen, Federal Republic of Germany.
J Biol Chem. 1993 Apr 5;268(10):7414-21.
Ribonucleoparticle-independent transport of precursor proteins into mammalian microsomes is stimulated by 70-kDa heat shock proteins (Hsc70) and an additional cytosolic protein. Here we addressed the question of whether other molecular chaperones can replace Hsc70 in facilitating protein transport into the endoplasmic reticulum. Specifically, we asked if members of the same family of stress proteins, i.e. the microsomal protein immunoglobulin heavy chain binding protein or the bacterial protein DnaK, can substitute for Hsc70. Furthermore, we investigated whether molecular chaperones with a proven role in protein folding and belonging to the other two major families of stress proteins, i.e. Hsp60 or Hsp90, can substitute for Hsc70. We show that none of these stress proteins was able to substitute for Hsc70 in facilitating protein transport into mammalian microsomes. GroEL (the bacterial member of the Hsp60 family) and Hsp90, however, competed with Hsc70 for binding of the non-native precursor protein. Therefore, we conclude that there are both substrate and functional specificity in the action of molecular chaperones.
70 kDa热休克蛋白（Hsc70）和另一种胞质蛋白可刺激前体蛋白以不依赖核糖核蛋白颗粒的方式转运至哺乳动物微粒体中。在此，我们探讨了其他分子伴侣是否能够在促进蛋白质转运至内质网的过程中替代Hsc70这一问题。具体而言，我们研究了应激蛋白同一家族的成员，即微粒体蛋白免疫球蛋白重链结合蛋白或细菌蛋白DnaK，是否能够替代Hsc70。此外，我们还研究了在蛋白质折叠过程中已证实发挥作用且属于另外两个主要应激蛋白家族的分子伴侣，即Hsp60或Hsp90，是否能够替代Hsc70。我们发现，这些应激蛋白均无法在促进蛋白质转运至哺乳动物微粒体的过程中替代Hsc70。然而，GroEL（Hsp60家族的细菌成员）和Hsp90与Hsc70竞争结合未折叠的前体蛋白。因此，我们得出结论，分子伴侣的作用存在底物和功能特异性。
