Degrons in protein substrates program the speed and operating efficiency of the AAA plus Lon proteolytic machine
Degrons in protein substrates program the speed and operating efficiency of the AAA plus Lon proteolytic machine
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DOI：
10.1073/pnas.0910392106
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发表时间：
2009-11-03
影响因子：
11.1
通讯作者：
Sauer, Robert T.
中科院分区：
文献类型：
--
作者：
Gur, Eyal;Sauer, Robert T.
AAA+蛋白酶是一种以atp为燃料的机器，它通过降解标签结合蛋白质底物，必要时展开分子，然后将多肽转移到蛋白质水解室中。标签识别通常被视为一种被动反应。相比之下，对于AAA+ Lon蛋白酶，我们发现降解标签也是决定蛋白酶活性水平的调控元件。事实上，融合到同一蛋白质上的不同标签会使降解速度和能量效率提高10倍或更多。Degron与Lon六聚体中多个位点的结合似乎可以不同地稳定特定的酶构象，包括具有高蛋白酶和低atp酶活性的构象，并导致积极的协同降解。这些变构机制允许Lon在快速或缓慢的蛋白质水解模式下运作，根据特定的生理需要，并可能有助于最大限度地降解应激诱导变性后错误折叠的蛋白质。
AAA+ proteases are ATP-fueled machines that bind protein substrates via a degradation tag, unfold the molecule if necessary, and then translocate the polypeptide into a chamber for proteolysis. Tag recognition is normally viewed as a passive reaction. By contrast, for the AAA+ Lon protease, we show that degron tags are also regulatory elements that determine protease activity levels. Indeed, different tags fused to the same protein change degradation speeds and energetic efficiencies by 10-fold or more. Degron binding to multiple sites in the Lon hexamer appears to differentially stabilize specific enzyme conformations, including one with high protease and low ATPase activity, and results in positively cooperative degradation. These allosteric mechanisms allow Lon to operate in either a fast or slow proteolysis mode, according to specific physiological needs, and may help maximize degradation of misfolded proteins following stress-induced denaturation.