Investigations on the maturation and regulation of archaebacterial proteasomes
Investigations on the maturation and regulation of archaebacterial proteasomes
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DOI：
10.1016/s0022-2836(03)00080-9
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发表时间：
2003-03-14
影响因子：
5.6
通讯作者：
Huber, R
中科院分区：
文献类型：
--
作者：
Groll, M;Brandstetter, H;Huber, R
20 S蛋白酶体（核心颗粒，CP）是一种多功能蛋白酶复合物，由四个七聚体亚基环组成，排列在中空的桶形结构中。在这里，我们报告的晶体结构的CP从古生球菌fulgidus在2.25埃分辨率。该CP的早期和晚期组装中间体的结构的分析提供了新的见解，在古细菌CP的成熟，并表明在真核生物中观察到的组装中间体的相似性。我们还显示了一个显着的差异，真核和古细菌20 S蛋白酶体之间的机制和调节底物的访问。虽然真核CP通过施加具有特征性序列基序（YDR基序）的拓扑闭合而被外α环的N末端尾部自动抑制，并且显示出调节门控，但该区段在CP中是无序的，并且在A的α（7）亚复合物中具有不同的结构。闪烁体留下通向直径为13埃的颗粒的孔。突变和功能研究表明古细菌20 S蛋白酶体中不存在调控门控。(C)2003爱思唯尔科技有限公司版权所有。
The 20 S proteasome (core particle, CP) is a multifunctional protease complex and composed of four heptameric subunit rings arranged in a hollow, barrel-shaped structure. Here, we report the crystal structure of the CP from Archaeoglobus fulgidus at 2.25 Angstrom resolution. The analysis of the structure of early and late assembly intermediates of this CP gives new insights in the maturation of archaebacterial CPs and indicates similarities to assembly intermediates observed in eukaryotes. We also show a striking difference in mechanism and regulation of substrate access between eukaryotic and archaebacterial 20 S proteasomes. While eukaryotic CPs are auto-inhibited by the N-terminal tails of the outer a-ring by imposing topological closure with a characteristic sequence motif (YDR-motif) and show regulatory gating this segment is disordered in the CP and differently structured in the alpha(7)-sub-complex of A. fulgidus leaving a pore leading into the particle with a diameter of 13 Angstrom. Mutagenesis and functional studies indicate the absence of regulatory gating in the archaeal 20 S proteasome. (C) 2003 Elsevier Science Ltd. All rights reserved.