The Proteasomal ATPases Use a Slow but Highly Processive Strategy to Unfold Proteins.
The Proteasomal ATPases Use a Slow but Highly Processive Strategy to Unfold Proteins.
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DOI：
10.3389/fmolb.2017.00018
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发表时间：
2017
影响因子：
5
通讯作者：
Smith DM
中科院分区：
文献类型：
--
作者：
Snoberger A;Anderson RT;Smith DM
生命的所有领域都具有 ATP 依赖性区室化蛋白酶，将其肽酶位点隔离在其内部。 ATP 酶复合物通常会与这些区室化的蛋白酶结合，以便展开并将底物注入蛋白酶中进行降解。人们投入了大量精力来了解如何利用 ATP 水解作用对蛋白质施加作用力并使其展开。细菌 ATP 酶 ClpX 的展开动力学已被证明类似于一个快速马达，它捕获未折叠的中间体作为展开蛋白质的策略。在本研究中，我们试图确定真核生物和古细菌的蛋白酶体 ATP 酶是否表现出相似的解折叠动力学。我们发现，蛋白酶体 ATP 酶似乎对蛋白质展开使用不同的动力学策略，表现为较慢但更具持续性和高效的易位马达，特别是在遇到折叠结构域时。我们预计这些差异是由于 ATP 结合/交换循环的差异、反式精氨酸指的存在或穿线环（即 OB 结构域）的存在造成的，这些结构可用作刚性平台来拉动折叠结构域。我们推测这些差异可能是由于这些机器预计会遇到的不同客户端池而演变的。
All domains of life have ATP-dependent compartmentalized proteases that sequester their peptidase sites on their interior. ATPase complexes will often associate with these compartmentalized proteases in order to unfold and inject substrates into the protease for degradation. Significant effort has been put into understanding how ATP hydrolysis is used to apply force to proteins and cause them to unfold. The unfolding kinetics of the bacterial ATPase, ClpX, have been shown to resemble a fast motor that traps unfolded intermediates as a strategy to unfold proteins. In the present study, we sought to determine if the proteasomal ATPases from eukaryotes and archaea exhibit similar unfolding kinetics. We found that the proteasomal ATPases appear to use a different kinetic strategy for protein unfolding, behaving as a slower but more processive and efficient translocation motor, particularly when encountering a folded domain. We expect that these dissimilarities are due to differences in the ATP binding/exchange cycle, the presence of a trans-arginine finger, or the presence of a threading ring (i.e., the OB domain), which may be used as a rigid platform to pull folded domains against. We speculate that these differences may have evolved due to the differing client pools these machines are expected to encounter.