Crystal structure of a chaperone complex that contributes to the assembly of yeast 20S proteasomes

Eukaryotic 20S proteasomes are composed of two alpha-rings and two beta-rings, which form an alpha beta beta alpha stacked structure. Here we describe a proteasome-specific chaperone complex, designated Dmp1-Dmp2, in budding yeast. Dmp1-Dmp2 directly bound to the alpha 5 subunit to facilitate alpha-ring formation. In Delta dmp1 cells, alpha-rings lacking alpha 4 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-alpha 5 complex reveals how this chaperone functions in proteasome assembly and why it dissociates from proteasome precursors before the b-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，形成一种αββα的堆叠结构。在此我们描述了在芽殖酵母中一种蛋白酶体特异性的伴侣复合物，被命名为Dmp1 - Dmp2。Dmp1 - Dmp2直接与α5亚基结合以促进α环的形成。在Δdmp1细胞中，观察到缺乏α4的α环以及20S蛋白酶体形成减少。Dmp1 - Dmp2在蛋白酶体组装的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（一种哺乳动物的蛋白酶体组装伴侣）非常相似；然而，Dmp1和Dmp2与PAC3均未显示出明显的序列相似性。Dmp1 - Dmp2 - α5复合物的结构揭示了这种伴侣在蛋白酶体组装中如何发挥作用，以及为什么它在β环组装之前从蛋白酶体前体上解离。