Endoproteolytic activity of the proteasome
Endoproteolytic activity of the proteasome
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DOI：
10.1126/science.1079293
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发表时间：
2003-01-17
期刊：
影响因子：
56.9
通讯作者：
Thomas, PJ
中科院分区：
文献类型：
--
作者：
Liu, CW;Corboy, MJ;Thomas, PJ
蛋白酶体在调节蛋白和错误折叠蛋白的降解中发挥着核心作用。目前的模型表明，底物通过将其末端逐步穿过门控底物通道来进入内部催化位点。在这里，我们发现潜在的（封闭的）和活化的（开放的）蛋白酶体会降解内部肽键处的两个天然无序的底物，即使它们缺乏可及的末端，这表明这些底物本身促进了蛋白酶体的门控。这种内切蛋白水解作用提供了一种从无活性前体调节转录因子释放的分子机制，以及一种获取错误折叠多域蛋白内部折叠缺陷的方法。
The proteasome plays a central role in the degradation of regulatory and misfolded proteins. Current models suggest that substrates access the internal catalytic sites by processively threading their termini through the gated substrate channel. Here, we found that latent (closed) and activated (open) proteasomes degraded two natively disordered substrates at internal peptide bonds even when they lacked accessible termini, suggesting that these substrates themselves promoted gating of the proteasome. This endoproteolysis provides a molecular mechanism for regulated release of transcription factors from inactive precursors as well as a means of accessing internal folding defects of misfolded multidomain proteins.