Emeritus Group Structure Research, Max Planck Institut für Biochemie, 82152 Martinsried, Germany;Center for Integrated Protein Science at the Department Chemie, Lehrstuhl für Biochemie, Technische Unversität München, 85748 Garching, Germany;
Center for Integrated Protein Science at the Department Chemie, Lehrstuhl für Biochemie, Technische Unversität München, 85748 Garching, Germany;
Proc Natl Acad Sci U S A. 2014 Jul 1;111(26):9479-84. doi: 10.1073/pnas.1408018111. Epub 2014 Jun 16.
Two clusters of configurations of the main proteolytic subunit β5 were identified by principal component analysis of crystal structures of the yeast proteasome core particle (yCP). The apo-cluster encompasses unliganded species and complexes with nonpeptidic ligands, and the pep-cluster comprises complexes with peptidic ligands. The murine constitutive CP structures conform to the yeast system, with the apo-form settled in the apo-cluster and the PR-957 (a peptidic ligand) complex in the pep-cluster. In striking contrast, the murine immune CP classifies into the pep-cluster in both the apo and the PR-957-liganded species. The two clusters differ essentially by multiple small structural changes and a domain motion enabling enclosure of the peptidic ligand and formation of specific hydrogen bonds in the pep-cluster. The immune CP species is in optimal peptide binding configuration also in its apo form. This favors productive ligand binding and may help to explain the generally increased functional activity of the immunoproteasome. Molecular dynamics simulations of the representative murine species are consistent with the experimentally observed configurations. A comparison of all 28 subunits of the unliganded species with the peptidic liganded forms demonstrates a greatly enhanced plasticity of β5 and suggests specific signaling pathways to other subunits.
通过对酵母蛋白酶体核心颗粒（yCP）晶体结构的主成分分析，鉴定出主要蛋白酶体亚基β5 的两个结构簇。无配体簇包含未配位的物种和与非肽配体的复合物，而肽簇则包含与肽配体的复合物。鼠源组成型 CP 结构与酵母系统一致，apo 形式位于 apo 簇中，PR-957（一种肽配体）复合物位于 pep 簇中。相比之下，鼠源免疫 CP 在 apo 和 PR-957 配体物种中均归类于 pep 簇。这两个结构簇主要通过多种小的结构变化和结构域运动来区分，这些变化使肽配体得以封闭，并在 pep 簇中形成特定的氢键。免疫 CP 物种在 apo 形式下也处于最佳的肽结合构象。这有利于有效配体结合，并可能有助于解释免疫蛋白酶体通常增加的功能活性。代表性鼠源的分子动力学模拟与实验观察到的结构一致。将无配体物种的所有 28 个亚基与肽配体形式进行比较，表明β5 的可塑性大大增强，并暗示存在特定的信号转导途径到其他亚基。
