Knowlton J R, Johnston S C, Whitby F G, Realini C, Zhang Z, Rechsteiner M, Hill C P
Department of Biochemistry, University of Utah, Salt Lake City 84132, USA.
Nature. 1997 Dec 11;390(6660):639-43. doi: 10.1038/37670.
The specificity of the 20S proteasome, which degrades many intracellular proteins, is regulated by protein complexes that bind to one or both ends of the cylindrical proteasome structure. One of these regulatory complexes, the 11S regulator (known as REG or PA28), stimulates proteasome peptidase activity and enhances the production of antigenic peptides for presentation by class I molecules of the major histocompatibility complex (MHC). The three REG subunits that have been identified, REGalpha, REGbeta and REGgamma (also known as the Ki antigen), share extensive sequence similarity, apart from a highly variable internal segment of 17-34 residues which may confer subunit-specific properties. REGalpha and REGbeta preferentially form a heteromeric complex, although purified REGalpha forms a heptamer in solution and has biochemical properties similar to the heteromeric REGalpha/REGbeta complex. We have now determined the crystal structure of human recombinant REGalpha at 2.8 A resolution. The heptameric barrel-shaped assembly contains a central channel that has an opening of 20 A diameter at one end and another of 30 A diameter at the presumed proteasome-binding surface. The binding of REG probably causes conformational changes that open a pore in the proteasome alpha-subunits through which substrates and products can pass.
20S蛋白酶体可降解多种细胞内蛋白质，其特异性受与圆柱形蛋白酶体结构一端或两端结合的蛋白质复合物调控。其中一种调控复合物，即11S调节因子（称为REG或PA28），可刺激蛋白酶体肽酶活性，并增强主要组织相容性复合体（MHC）I类分子呈递的抗原肽的产生。已鉴定出的三个REG亚基，REGα、REGβ和REGγ（也称为Ki抗原），除了一段17 - 34个残基的高度可变内部片段可能赋予亚基特异性特性外，它们具有广泛的序列相似性。REGα和REGβ优先形成异源复合物，尽管纯化的REGα在溶液中形成七聚体，且具有与异源REGα/REGβ复合物相似的生化特性。我们现已确定了人重组REGα在2.8埃分辨率下的晶体结构。七聚体桶状组装体包含一个中央通道，该通道一端的开口直径为20埃，在假定的蛋白酶体结合表面的另一端开口直径为30埃。REG的结合可能会引起构象变化，从而在蛋白酶体α亚基中打开一个孔，底物和产物可通过该孔。
