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首页> 外文期刊>Journal of Molecular Biology >Conformational constraints for protein self-cleavage in the proteasome
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Conformational constraints for protein self-cleavage in the proteasome

机译：蛋白酶体中蛋白质自我切割的构象约束

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The proteasome is the central enzyme of protein degradation in the cytosol and the nucleus. It is involved in the removal of abnormal, misfolded or incorrectly assembled proteins, in the processing or degradation of transcriptional regulators in stress response, in degradation of cyclins in cell-cycle control, in the destruction of transcription factors or metabolic enzymes in cell differentiation and metabolic response, and in MHC class I mediated cellular immune response. By the analysis of the crystal and molecular structures of the 20 S proteasomes from the archaeon Thermoplasma acidophilum and from yeast it was shown that the beta-type subunits in which the proteolytic activities reside are members of the N-terminal nucleophile (Ntn) protein family. They are synthesized as proproteins and become active by autoprocessing at a Gly-1-Thr1 bond. The Thr1Ala mutant of subunit beta1/Pre3 of the 20 S proteasome from yeast is unable to autolyse. Its crystal and molecular structure at 2.2 Angstrom resolution described here shows that the pro-segment adopts a well-defined gamma-turn conformation at Gly-1 and provides a first view at an autolysis site in Ntn hydrolases. The Gly-1 carbonyl oxygen displays two hydrogen bonds. The modelled Thr1 side-chain is located above the gamma-turn bulge such that addition of its nucleophilic hydroxyl group to the electrophilic Gly-1 carbonyl carbon atom may proceed by very small motions. The pro-segment binding site and the catalytic site provide a rigid structural framework and appropriate hydrogen bond donors for this reaction. The same structure also supports addition of the Thr1 hydroxyl group to the carbonyl carbon atom of Leu-2 as a model for the first step in substrate hydrolysis by the proteasome. (C) 1998 Academic Press. [References: 21]
机译：蛋白酶体是细胞质和细胞核中蛋白质降解的中心酶。它涉及清除异常，折叠错误或组装错误的蛋白质，应激反应中转录调节剂的加工或降解，细胞周期控制中细胞周期蛋白的降解，细胞分化和再生过程中转录因子或代谢酶的破坏。代谢反应，以及在MHC I类介导的细胞免疫反应中。通过分析古细菌嗜酸嗜热菌和酵母中20 S蛋白酶体的晶体和分子结构，表明其中存在蛋白水解活性的β型亚基是N末端亲核蛋白（Ntn）蛋白家族的成员。 。它们被合成为前蛋白，并通过在Gly-1-Thr1键上进行自动加工而变得活跃。来自酵母的20 S蛋白酶体beta1 / Pre3亚基的Thr1Ala突变体无法自溶。此处描述的其在2.2埃分辨率下的晶体和分子结构表明，该前段在Gly-1处采用了明确定义的γ-转构象，并在Ntn水解酶的自溶位点提供了第一个视图。 Gly-1羰基氧具有两个氢键。建模的Thr1侧链位于伽马转凸起上方，因此其亲核羟基向亲电Gly-1羰基碳原子的加成可以通过很小的运动进行。前段结合位点和催化位点为该反应提供了刚性的结构框架和合适的氢键供体。相同的结构还支持将Thr1羟基加到Leu-2的羰基碳原子上，作为蛋白酶体水解底物的第一步的模型。 （C）1998年学术出版社。 [参考：21]

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