Yashiroda Hideki, Mizushima Tsunehiro, Okamoto Kenta, Kameyama Tomie, Hayashi Hidemi, Kishimoto Toshihiko, Niwa Shin-ichiro, Kasahara Masanori, Kurimoto Eiji, Sakata Eri, Takagi Kenji, Suzuki Atsuo, Hirano Yuko, Murata Shigeo, Kato Koichi, Yamane Takashi, Tanaka Keiji
Laboratory of Frontier Science, Core Technology and Research Center, Tokyo Metropolitan Institute of Medical Science, Bunkyo-ku, Tokyo 113-8613, Japan.
Nat Struct Mol Biol. 2008 Mar;15(3):228-36. doi: 10.1038/nsmb.1386. Epub 2008 Feb 17.
Eukaryotic 20S proteasomes are composed of two alpha-rings and two beta-rings, which form an alphabetabetaalpha stacked structure. Here we describe a proteasome-specific chaperone complex, designated Dmp1-Dmp2, in budding yeast. Dmp1-Dmp2 directly bound to the alpha5 subunit to facilitate alpha-ring formation. In Deltadmp1 cells, alpha-rings lacking alpha4 and decreased formation of 20S proteasomes were observed. Dmp1-Dmp2 interacted with proteasome precursors early during proteasome assembly and dissociated from the precursors before the formation of half-proteasomes. Notably, the crystallographic structures of Dmp1 and Dmp2 closely resemble that of PAC3-a mammalian proteasome-assembling chaperone; nonetheless, neither Dmp1 nor Dmp2 showed obvious sequence similarity to PAC3. The structure of the Dmp1-Dmp2-alpha5 complex reveals how this chaperone functions in proteasome assembly and why it dissociates from proteasome precursors before the beta-rings are assembled.
真核生物的20S蛋白酶体由两个α环和两个β环组成，形成αβα堆叠结构。在此，我们描述了一种在芽殖酵母中名为Dmp1 - Dmp2的蛋白酶体特异性伴侣复合体。Dmp1 - Dmp2直接与α5亚基结合以促进α环的形成。在缺失Dmp1的细胞中，观察到缺少α4的α环以及20S蛋白酶体形成减少。Dmp1 - Dmp2在蛋白酶体组装早期与蛋白酶体前体相互作用，并在半蛋白酶体形成之前从这些前体上解离。值得注意的是，Dmp1和Dmp2的晶体结构与PAC3（一种哺乳动物蛋白酶体组装伴侣）的晶体结构非常相似；然而，Dmp1和Dmp2与PAC3均无明显的序列相似性。Dmp1 - Dmp2 - α5复合体的结构揭示了这种伴侣蛋白在蛋白酶体组装中的作用方式以及它在β环组装之前从蛋白酶体前体上解离的原因。
