Mechanism of gate opening in the 20S proteasome by the proteasomal ATPases
Mechanism of gate opening in the 20S proteasome by the proteasomal ATPases
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DOI：
10.1016/j.molcel.2008.03.004
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发表时间：
2008-05-09
期刊：
影响因子：
16
通讯作者：
Cheng, Yifan
中科院分区：
文献类型：
--
作者：
Rabl, Julius;Smith, David M.;Cheng, Yifan
底物通过一个门控通道进入圆柱形的20S蛋白酶体，该通道受真核生物中19S调控颗粒中的ATPase或古生物中同源的PAN ATPase复合体的调控。这些ATPase含有一个保守的C-末端疏水酪氨酸-X(HbYX)基序，可以在与ATP结合时触发门的打开。使用冷冻电子显微镜，我们确定了古生菌20S中PAN的C-末端残基结合的位置，并确定了闭合和开放形式的门的结构。含有HbYX基序的多肽与相邻阿尔法亚基之间的口袋中的20S结合，在那里它们与开门所需的保守残基相互作用。这种相互作用导致阿尔法亚基的旋转和反转环路的位移，从而稳定了打开门的构象。这一机制与PA26/28的机制不同，PA26/28缺乏HbYX基序，不会导致α亚基旋转。这些发现证明了ATPase的C末端是如何促进底物进入的。
Substrates enter the cylindrical 20S proteasome through a gated channel that is regulated by the ATPases in the 19S regulatory particle in eukaryotes or the homologous PAN ATPase complex in archaea. These ATPases contain a conserved C-terminal hydrophobic-tyrosine-X (HbYX) motif that triggers gate opening upon ATP binding. Using cryo-electron microscopy, we identified the sites in the archaeal 20S where PAN's C-terminal residues bind and determined the structures of the gate in its closed and open forms. Peptides containing the HbYX motif bind to 20S in the pockets between neighboring alpha subunits where they interact with conserved residues required for gate opening. This interaction induces a rotation in the alpha subunits and displacement of a reverse-turn loop that stabilizes the open-gate conformation. This mechanism differs from that of PA26/28, which lacks the HbYX motif and does not cause alpha subunit rotation. These findings demonstrated how the ATPases' C termini function to facilitate substrate entry.