An asymmetric interface between the regulatory and core particles of the proteasome
An asymmetric interface between the regulatory and core particles of the proteasome
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DOI：
10.1038/nsmb.2147
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发表时间：
2011-11-01
影响因子：
16.8
通讯作者：
Finley, Daniel
中科院分区：
文献类型：
--
作者：
Tian, Geng;Park, Soyeon;Finley, Daniel
酿酒酵母蛋白酶体由19个亚基调控颗粒和28个亚基核心颗粒组成。要被降解，底物必须穿过核心颗粒-调节颗粒界面，这是复杂构象变化和调节事件的场所。该界面包括两个排列的异构环，一个由调节粒子的6个ATPase(RPT)亚基形成，另一个由核心粒子的7个a亚基形成。RPT C末端与α环上的亚基间腔结合，从而指导核心颗粒门控和蛋白酶体组装。我们使用一种交联法将RPT C末端映射到a亚单位口袋，揭示了一种意想不到的不对称：环的一侧显示Rpt2-α4、Rpt6-α3和Rpt3-α2的1：1接触，而在相反的一侧，Rpt1、Rpt4和Rpt5的尾部分别交叉连接到多个a口袋。RPT-核心颗粒交联物都对核苷酸敏感，这意味着ATP水解驱动核心颗粒-调节颗粒界面的动态变化。
The Saccharomyces cerevisiae proteasome comprises a 19-subunit regulatory particle and a 28-subunit core particle. To be degraded, substrates must cross the core particle-regulatory particle interface, a site for complex conformational changes and regulatory events. This interface includes two aligned heteromeric rings, one formed by the six ATPase (Rpt) subunits of the regulatory particle and the other by the seven a subunits of the core particle. The Rpt C termini bind to intersubunit cavities in the alpha-ring, thus directing core particle gating and proteasome assembly. We mapped the Rpt C termini to the a subunit pockets, using a cross-linking approach that revealed an unexpected asymmetry: one side of the ring shows 1:1 contacts of Rpt2-alpha 4, Rpt6-alpha 3 and Rpt3-alpha 2, whereas on the opposite side, the Rpt1, Rpt4 and Rpt5 tails each cross-link to multiple a pockets. Rpt-core particle cross-links are all sensitive to nucleotides, implying that ATP hydrolysis drives dynamic alterations at the core particle-regulatory particle interface.