Jayarapu Krupakar, Griffin Thomas A
William S. Rowe Division of Rheumatology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
Biochem Biophys Res Commun. 2007 Jul 6;358(3):867-72. doi: 10.1016/j.bbrc.2007.05.011. Epub 2007 May 11.
Animals with immune systems have two types of proteasomes, "standard proteasomes" and "immunoproteasomes" that respectively contain constitutively expressed catalytic subunits or interferon-gamma-inducible catalytic subunits. Interestingly, proteasome assembly is biased against formation of most mixed proteasomes containing combinations of standard subunits and immunosubunits. We previously demonstrated that catalytic subunit propeptide differences contribute to this assembly specificity. In the current study, we investigated the contributions of catalytic subunit propeptides and C-terminal extensions to intra-proteasome protein-protein interactions that are potentially involved in mediating biased assembly of human proteasomes, and we found a number of interactions that differentially depended on these structures. For example, the C-terminal extension of standard subunit beta2 is required for beta2's interaction with adjacent beta3, whereas the C-terminal extension of immunosubunit beta2i is dispensable for beta2i's interaction with beta3. Taken together, our results suggest mechanisms whereby differential intra-proteasome interactions could contribute to proteasome assembly specificity.
具有免疫系统的动物有两种类型的蛋白酶体，即“标准蛋白酶体”和“免疫蛋白酶体”，它们分别含有组成型表达的催化亚基或干扰素-γ诱导的催化亚基。有趣的是，蛋白酶体组装倾向于不形成大多数包含标准亚基和免疫亚基组合的混合蛋白酶体。我们之前证明催化亚基前肽差异导致了这种组装特异性。在当前研究中，我们研究了催化亚基前肽和C末端延伸对蛋白酶体内蛋白质-蛋白质相互作用的贡献，这些相互作用可能参与介导人类蛋白酶体的偏向组装，并且我们发现了一些差异依赖于这些结构的相互作用。例如，标准亚基β2的C末端延伸是β2与相邻β3相互作用所必需的，而免疫亚基β2i的C末端延伸对于β2i与β3的相互作用是可有可无的。综上所述，我们的结果表明蛋白酶体内差异相互作用可能导致蛋白酶体组装特异性的机制。
