Modelling proteasome and proteasome regulator activities.
Modelling proteasome and proteasome regulator activities.
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DOI：
10.3390/biom4020585
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发表时间：
2014-06-20
期刊：
影响因子：
5.5
通讯作者：
Mishto M
中科院分区：
文献类型：
--
作者：
Liepe J;Holzhütter HG;Kloetzel PM;Stumpf MP;Mishto M
蛋白酶体是一种关键的蛋白水解酶，参与多种过程，从清除受损的蛋白质到呈递抗原到CD8+T淋巴细胞。靶蛋白中使用了哪些切割位点以及这些蛋白被降解的速度对免疫系统功能和许多细胞代谢过程都有深远的影响。蛋白酶体活性的调节涉及不同的机制，如催化亚基的替代、调节复合体与蛋白酶体门的结合以及由靶蛋白本身引发的蛋白酶体构象改变。数学模型在分析中具有不可估量的价值，并有可能使我们能够预测蛋白酶体调节机制的复杂相互作用，以及蛋白质降解率和MHC I类表位生成的最终结果。本文综述了对蛋白酶体活性、切割偏好变异及其调节机制之一的修饰进行数学建模的开创性尝试。
Proteasomes are key proteases involved in a variety of processes ranging from the clearance of damaged proteins to the presentation of antigens to CD8+ T-lymphocytes. Which cleavage sites are used within the target proteins and how fast these proteins are degraded have a profound impact on immune system function and many cellular metabolic processes. The regulation of proteasome activity involves different mechanisms, such as the substitution of the catalytic subunits, the binding of regulatory complexes to proteasome gates and the proteasome conformational modifications triggered by the target protein itself. Mathematical models are invaluable in the analysis; and potentially allow us to predict the complex interactions of proteasome regulatory mechanisms and the final outcomes of the protein degradation rate and MHC class I epitope generation. The pioneering attempts that have been made to mathematically model proteasome activity, cleavage preference variation and their modification by one of the regulatory mechanisms are reviewed here.